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Cited by 224Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersAdolescent and Pediatric Healthcare

Clinical practice guidelines for the care of girls and women with Turner syndrome.

Open access
Gravholt, Claus H, Andersen, Niels H, Christin-Maitre, Sophie, Davis, Shanlee M, Duijnhouwer, Anthonie, Gawlik, Aneta, Maciel-Guerra, Andrea T, Gutmark-Little, Iris +68 more·2024·European Journal of Endocrinology
DOI 10.1093/ejendo/lvae050PMC PMC11759048
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Abstract

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

AI snapshot

Written from a shortened version of the paper’s full text (it is longer than we read).

TL;DR

This 2024 international clinical practice guideline updates care for girls and women with Turner syndrome across diagnosis/genetics, growth, puberty and estrogen treatment, cardiovascular health, transition, fertility, comorbidities, and neurocognition. It provides graded recommendations, but only four clinical questions were formally GRADE-evaluated, with many recommendations based on expert consensus.

Key findings

  • Turner syndrome affects 50 per 100 000 females (abstract; the introduction says 25-50 per 100 000) and requires multidisciplinary care across the lifespan; the guideline covers eight domains and includes new advances in diagnostics/genetics, estrogen treatment, fertility, comorbidities, and neurocognition/neuropsychology.
  • For growth, the guideline recommends GH starting at 45-50 µg kg−1 day−1 (1.3-1.5 mg m−2 day−1), increasing to a maximum of 68 µg kg−1 day−1 (2.0 mg m−2 day−1) if response is suboptimal; it reports adult height gains of approximately 5-8 cm, a meta-analysis mean gain of 7.2 cm, and normal adult height in 40%-50% of treated vs 4%-16% of non-GH-treated individuals in long-term controlled trials.
  • Cardiovascular findings include CHD prevalence of 40%-60%, BAV in more than 25%, and aortic dissection incidence of approximately 164 per 100 000 person-years vs 6 per 100 000 person-years in the general population; the guideline recommends lifelong surveillance, aortic size indexing (AHI, ASI, Z-score), blood pressure control, and pregnancy-specific cardiovascular management.
  • For puberty and fertility, the guideline recommends measuring LH, FSH, and AMH at 8-9 years and yearly until 11-12 years, initiating low-dose estrogen at 11-12 years if FSH is elevated on at least two measurements, preferring transdermal E2, adding cyclic progesterone after breakthrough bleeding, and offering oocyte cryopreservation as the primary fertility preservation option for post-menarche individuals of appropriate maturity; ovarian tissue cryopreservation should only be offered under ethics board approval.

Methods

  • The guideline was developed by an international working group initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, with eight groups addressing diagnosis/genetics, growth, puberty/estrogen, cardiovascular health, transition, fertility, comorbidities, and neurocognition; exploratory meetings were held in 2021 and a consensus meeting in Aarhus, Denmark in June 2023.
  • Four clinical questions—growth-promoting treatment, probability of viable pregnancy after oocyte donation, effects of blood pressure treatment, and optimal estrogen replacement—underwent formal GRADE evaluation with systematic literature searches in PubMed, Embase, and the Cochrane Library; other recommendations were derived from majority consensus or expert opinion and graded with the same evidence symbols.
  • Recommendations are worded as “recommend” (strong) or “suggest” (weak), with evidence quality classified from very low to strong.

Limitations

  • The paper states that formal evidence syntheses and grading were performed only for four GRADE questions; all other recommendations were based on majority consensus or expert opinion, and some GRADE questions had insufficient evidence—for example, no comparative studies of antihypertensive treatments or blood pressure targets in Turner syndrome were identified.
  • The paper notes that many areas lack rigorous long-term prospective studies, including optimal estrogen route/dose, progesterone regimens, fertility preservation outcomes, and transition outcomes; recommendations often rely on limited data and extrapolation from non-Turner populations.
  • Evident from the text: this is a clinical practice guideline, not a primary empirical study, and several recommendations are ungraded Good Practice Statements.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/ejendo/lvae050

Cites

920 of 920 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 1081 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Only two of these trials have followed non-GH-treated participants to adult height.

    “and only two of these trials have followed non-GH-treated participants to adult height.158,160”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [158] Stephure, 2005, Impact of growth hormone supplementation on adult height in Turner syndrome: results of the Canadian randomized controlled trial, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [160] Ross, 2011, Growth hormone plus childhood low-dose estrogen in Turner's syndrome, N Engl J Med source

      Not checked in the free run.

  • Findingcitation

    Only six RCTs have compared GH treatment with concurrent non-treatment or placebo control for at least one year.

    “Despite numerous studies of GH treatment in TS, only six randomized, controlled trials (RCTs) have compared GH treatment with a concurrent non-treatment or placebo control for at least one year157-162”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [157] Kollmann, 2016

      Not checked in the free run.

    • cites [158] Stephure, 2005, Impact of growth hormone supplementation on adult height in Turner syndrome: results of the Canadian randomized controlled trial, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [159] Rosenfeld, 1998, Growth hormone therapy of Turner's syndrome: beneficial effect on adult height, J Pediatr source

      Not checked in the free run.

    • cites [160] Ross, 2011, Growth hormone plus childhood low-dose estrogen in Turner's syndrome, N Engl J Med source

      Not checked in the free run.

    • cites [161] Quigley, 2002, Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [162] Davenport, 2007, Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multi-center trial, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Findingown data

    In almost all countries, oral preparations of progesterone and progestins were available (95.9%).

    “In almost all countries, oral preparations of progesterone and progestins were available (95.9%).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Dydrogesterone (67%) and/or medroxyprogesterone acetate (67%) were generally available with transdermal progestins in 25% of centers.

    “Dydrogesterone (67%) and/or medroxyprogesterone acetate (67%) were generally available with TD progestins in 25% of centers.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The availability of estrogen and progesterone preparations varies greatly world-wide as determined by an online survey conducted by ESPE between May 2020 and October 2022.

    “The availability of estrogen and progesterone preparations varies greatly world-wide as determined by an online survey conducted by ESPE between May 2020 and October 2022 (unpublished data submitted to Hormone Research in Paediatrics).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 245
  • Classified as probably not a substantial claim. 77
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    Although oral E2 preparations were widely available (82% of respondents), the lower doses of 1 and 0.5 mg tablets were only available in 40% and <10% of centers, respectively.

    “Although oral E2 preparations were widely available (82% of respondents), the lower doses of 1 and 0.5 mg tablets were only available in 40% and <10% of centers, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Transdermal E2 was the most widely available preparation (90%) and was the preferred option for pubertal induction in 69% of respondents.

    “TD E2 was the most widely available preparation (90%) and was the preferred option for pubertal induction in 69% of respondents.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Low dose ethinyl estradiol (2 mcg tablets) was available in nearly 50% of centers but was the preferred preparation in only 2.8%.

    “Low dose ethinyl estradiol (2 mcg tablets) was available in nearly 50% of centers but was the preferred preparation in only 2.8%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    For individuals with TS who do not have congenital or acquired cardiovascular disease, the current evidence is insufficient to make specific recommendations about competitive athletics.

    “For individuals with TS who do not have congenital or acquired cardiovascular disease, the current evidence is insufficient to make specific recommendations about competitive athletics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    There is no clear evidence for prophylactic medication during pregnancy in women with TS who have aortic dilation and no support for a specific type of anti-hypertensive medication.

    “There is no clear evidence for prophylactic medication during pregnancy in women with TS who have aortic dilation and no support for a specific type of anti-hypertensive medication.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The Endocrine Society TS-specific transition tool has been used in clinical research but has not yet been validated.

    “Another tool that has been used in clinical research but not yet validated is the TS-specific transition tool provided by the Endocrine Society (Table S8), which includes 10 questions about health, 16 about using health care, and 15 focused on social and emotional factors salient to TS.546”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [546] Patel, 2022, Patient-parent perceptions of transition readiness in Turner syndrome and associated factors, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Fewer women with TS had ever had sexual intercourse, and those who did were older at first intercourse.

    “Further, fewer women with TS had ever had sexual intercourse, and those who did were older at first intercourse.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [558] de Brouwer, 2022, First adolescent romantic and sexual experiences in individuals with differences of sex development/intersex conditions, J Adolesc Health source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Various healthcare transition models exist, ranging from adult and pediatric providers working within an integrated health care system, to completely separate settings/health systems and no structured hand-off process.

    “Various healthcare transition models exist, ranging from adult and pediatric providers working within an integrated health care system, to completely separate settings/health systems and no structured hand-off process.538”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [538] Bernard, 2019, MANAGEMENT OF ENDOCRINE DISEASE: transition of care for young adult patients with Turner syndrome, Eur J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In France, a one-day therapeutic small-group program for AYA with TS utilizing workshops focused on various aspects of health has been developed, but its impact is unclear.

    “In France, a one-day therapeutic small-group program for AYA with TS utilizing workshops focused on various aspects of health has been developed, but the impact of this program is unclear.538”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [538] Bernard, 2019, MANAGEMENT OF ENDOCRINE DISEASE: transition of care for young adult patients with Turner syndrome, Eur J Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    There is a lack of a unifying definition of a successful transition.

    “There is also a lack of a unifying definition of a “successful transition.””
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The PEERS program has modules targeted towards career building skills.

    “The PEERS program also has modules targeted towards career building skills.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Studies on the impact of transition interventions have been undertaken in a range of clinical settings, in different age groups, and with differing endpoints, limiting comparisons across studies.

    “Studies on the impact of transition interventions have been undertaken in a range of clinical settings, in different age groups, and with differing endpoints, limiting comparisons across studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    A survey showed most women with TS 18-25 years of age still relied on their parents for both care and finances, though independence increased with age.

    “Indeed, a survey showed most women with TS 18-25 years of age still relied on their parents for both care and finances, though independence increased with age.550”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [550] Streur, 2022, The transition to independence and adult care for women with Turner syndrome: current status and priorities of 1338 women and parents, Am J Med Genet A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    In many areas of the United States, specific services are either not available or not covered by payors for adults, including neuropsychological and audiologic testing, and access to occupational and speech therapies.

    “For example, in many areas of the United States specific services are either not available or not covered by payors for adults. This includes, but is not limited to, neuropsychological and audiologic testing, and access to occupational and speech therapies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The biggest improvement noted was a gain in confidence.

    “The biggest improvement noted was a gain in confidence.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Findings associated with an increased likelihood of identifying follicles in the ovarian cortex include mosaic karyotype with a 46,XX cell line, spontaneous puberty, measurable AMH, or FSH <10 IU/L.

    “Findings that may be associated with an increased likelihood of identifying follicles in the ovarian cortex include (1) mosaic karyotype with a 46,XX cell line, (2) spontaneous puberty, (3) measurable AMH or (4) FSH <10 IU L−1.263,578,579”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [578] Nadesapillai, 2023, Reproductive outcomes of women with Turner syndrome undergoing oocyte vitrification: a retrospective multicenter cohort study, J Clin Med source

      Not checked in the free run.

    • cites [579] Mamsen, 2019, Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Due to ovarian insufficiency, most individuals with TS are infertile, with spontaneous pregnancies occurring in about 10%.

    “Due to ovarian insufficiency, most individuals with TS are infertile, with spontaneous pregnancies occurring in about 10%.11,511,561-564”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [511] Calanchini, 2020, Fertility issues and pregnancy outcomes in Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [561] Bernard, 2016, Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome, Hum Reprod source

      Not checked in the free run.

    • cites [562] Birkebaek, 2002, Fertility and pregnancy outcome in Danish women with Turner syndrome, Clin Genet source

      Not checked in the free run.

    • cites [563] Hadnott, 2011, Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National institutes of health experience, Fertil Steril source

      Not checked in the free run.

    • cites [564] Słowikowska-Hilczer, 2017, Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the dsd-LIFE study, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In individuals with TS, AMH is associated with clinical features of ovarian reserve and has the strongest positive correlation with the presence of follicles in ovarian cortex tissue.

    “In individuals with TS, AMH is associated with clinical features of ovarian reserve270,581 and has the strongest positive correlation with the presence of follicles in ovarian cortex tissue .263,579,582”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [270] Lunding, 2015, AMH as predictor of premature ovarian insufficiency: a longitudinal study of 120 Turner syndrome patients, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [581] Hagen, 2010, Serum levels of anti-mullerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [579] Mamsen, 2019, Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation, Fertil Steril source

      Not checked in the free run.

    • cites [582] Nadesapillai, 2023, TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study, Fertil Steril source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The cost-benefit analysis of improving surveillance and diagnosis of comorbidities in individuals with TS remains to be determined.

    “The cost–benefit analysis of improving surveillance, and therefore diagnosis, of comorbidities in individuals with TS remains to be determined.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Pregnancies in individuals with TS are associated with a higher risk of maternal and fetal complications, as are pregnancies after oocyte donation in both TS and non-TS individuals.

    “Pregnancies in individuals with TS are associated with a higher risk of maternal and fetal complications as are pregnancies after oocyte donation in both TS and non-TS individuals.511,524,586”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [511] Calanchini, 2020, Fertility issues and pregnancy outcomes in Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [524] Hagman, 2013, Obstetric and neonatal outcome after oocyte donation in 106 women with Turner syndrome: a Nordic cohort study, Hum Reprod source

      Not checked in the free run.

    • cites [586] Keukens, 2022, Pre-eclampsia in pregnancies resulting from oocyte donation, natural conception or IVF: a systematic review and meta-analysis, Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The key predictive factors associated with the probability of spontaneous conception are a history of spontaneous menarche and a 45,X/46,XX karyotype.

    “The key predictive factors associated with the probability of spontaneous conception are a history of spontaneous menarche, and a 45,X/46,XX karyotype.11,511,561-563”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [511] Calanchini, 2020, Fertility issues and pregnancy outcomes in Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [561] Bernard, 2016, Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome, Hum Reprod source

      Not checked in the free run.

    • cites [562] Birkebaek, 2002, Fertility and pregnancy outcome in Danish women with Turner syndrome, Clin Genet source

      Not checked in the free run.

    • cites [563] Hadnott, 2011, Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National institutes of health experience, Fertil Steril source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Findingnone given

    Oocyte cryopreservation is preferentially offered to TS adolescents who experienced spontaneous menarche and are psychologically mature enough to understand and undergo the procedure.

    “Cryopreservation of oocytes is preferentially offered to TS adolescents who experienced spontaneous menarche and are psychologically mature enough to understand and undergo the procedure of ovarian hyperstimulation and oocyte retrieval.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The odds of preterm birth and small-for-gestational-age of infants born to individuals with TS compared with women in the general population are 3-fold and 5-fold greater, respectively.

    “The odds of a preterm birth and small-for-gestational-age of infants born to individuals with TS compared with women in the general population are 3-fold and 5-fold greater, respectively.590”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [590] Ramage, 2020, Maternal, pregnancy, and neonatal outcomes for women with Turner syndrome, Birth Defects Res source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    OTC is an established procedure for women facing gonadotoxic therapy, but little is known about its utility in conditions with a chromosomal abnormality associated with underlying ovarian dysgenesis such as TS.

    “Although, OTC is an established procedure for women facing gonadotoxic therapy,613 little is known about its utility in conditions when a chromosomal abnormality that is associated with underlying ovarian dysgenesis such as TS is present.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [613] Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org, 2019, Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Reported anomalies in TS pregnancies include cerebral palsy, neuropsychological disorders, cleft lip and palate, coarctation of the aorta, ambiguous genitalia, hydrocephalus, and trisomy 21.

    “Reported anomalies include cerebral palsy, neuropsychological disorders, cleft lip and palate, coarctation of the aorta, ambiguous genitalia, hydrocephalus as well as trisomy 21.11,562,563”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [562] Birkebaek, 2002, Fertility and pregnancy outcome in Danish women with Turner syndrome, Clin Genet source

      Not checked in the free run.

    • cites [563] Hadnott, 2011, Outcomes of spontaneous and assisted pregnancies in Turner syndrome: the U.S. National institutes of health experience, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Successful cryopreservation of mature oocytes has been reported in a greater proportion of individuals with TS with mosaic karyotypes, but there are also reports of oocyte vitrification in individuals with monosomy X, including cases with decreased AMH.

    “While the successful cryopreservation of mature oocytes has been reported in a greater proportion of individuals with TS with mosaic karyotypes, there are also reports of oocyte vitrification in individuals with monosomy X, including cases with a decreased AMH.597,598”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [597] Talaulikar, 2019, Outcome of ovarian stimulation for oocyte cryopreservation in women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [598] Vergier, 2019, Fertility preservation in Turner syndrome: karyotype does not predict ovarian response to stimulation, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    These factors have been proposed as predictors of successful oocyte cryopreservation, but discrepancies remain.

    “While these factors have been proposed as predictors of successful oocyte cryopreservation, discrepancies remain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Recent publications describe oocyte preservation in minors; the youngest girl was 7 years old.

    “Recent publications describe oocyte preservation in minors; the youngest girl was 7 years old.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [599] Martel, 2022, The use of oocyte cryopreservation for fertility preservation in patients with sex chromosome disorders: a case series describing outcomes, J Assist Reprod Genet source

      Not checked in the free run.

    • cites [602] Azem, 2020, Bypassing physiological puberty, a novel procedure of oocyte cryopreservation at age 7: a case report and review of the literature, Fertil Steril source

      Not checked in the free run.

    • cites [611] Gayete-Lafuente, 2023, Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency, J Assist Reprod Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The success rate of pregnancy using cryopreserved oocytes or OTC is unknown, because there is only one reported live birth after use of cryopreserved oocytes and one recorded pregnancy after OTC in TS.

    “The success rate of pregnancy of using cryopreserved oocytes or OTC is unknown, because there is only one reported live birth after use of cryopreserved oocytes591 and one recorded pregnancy after OTC in TS.592”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [591] Strypstein, 2022, First live birth after fertility preservation using vitrification of oocytes in a woman with mosaic Turner syndrome, J Assist Reprod Genet source

      Not checked in the free run.

    • cites [592] Dunlop, 2023, Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex, J Assist Reprod Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Individuals with mosaic TS are more likely to have spontaneous puberty, normal gonadotropin levels, measurable AMH, and follicles in ovarian biopsies compared to those with monosomy X karyotype.

    “Individuals with mosaic TS are more likely to have spontaneous puberty, normal gonadotropin levels, a measurable AMH, and follicles in ovarian biopsies as compared to those who have monosomy X karyotype.263,579,608”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [579] Mamsen, 2019, Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation, Fertil Steril source

      Not checked in the free run.

    • cites [608] Nadesapillai, 2021, The challenge of defining predictive parameters for fertility preservation counseling in young females with Turner syndrome, Acta Obstet Gynecol Scand source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Data are inconsistent regarding the risk of birth anomalies, which are reported in 0%-24% of spontaneous TS pregnancies compared with ∼3% in the background population.

    “Data are inconsistent regarding the risk of birth anomalies, which are reported in 0%-24% of spontaneous TS pregnancies compared with ∼3% in the background population.11,511,561,562,584,589”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [511] Calanchini, 2020, Fertility issues and pregnancy outcomes in Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [561] Bernard, 2016, Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome, Hum Reprod source

      Not checked in the free run.

    • cites [562] Birkebaek, 2002, Fertility and pregnancy outcome in Danish women with Turner syndrome, Clin Genet source

      Not checked in the free run.

    • cites [584] Tarani, 1998, Pregnancy in patients with Turner's syndrome: six new cases and review of literature, Gynecol Endocrinol source

      Not checked in the free run.

    • cites [589] Hagman, 2011, Obstetric outcomes in women with Turner karyotype, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The follicle density of xenografts from ovaries of prepubertal girls with TS was significantly higher than that of pubertal girls with TS and was comparable to that of age-matched controls.

    “The follicle density of xenografts from ovaries of prepubertal girls with TS was significantly higher than that of pubertal girls with TS and was comparable to that of age-matched controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [609] Peek, 2023, Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Nadesapillai et al. performed a unilateral ovariectomy in 93 patients; in 30/93 (32%) follicles were found.

    “Nadesapillai et al. performed a unilateral ovariectomy in 93 patients; in 30/93 (32%) follicles were found.263,582”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [582] Nadesapillai, 2023, TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Initial ovarian reserve in girls with TS is already limited, while the follicular loss after OTT is more than 50%, due to ischemia in transplanted tissue during the first days after the procedure.

    “However, initial ovarian reserve in girls with TS is already limited, while the follicular loss after OTT is more than 50%, due to ischemia in in transplanted tissue during the first days after the procedure.620,621”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [620] Baird, 1999, Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196 C, Endocrinology source

      Not checked in the free run.

    • cites [621] Cacciottola, 2021, Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes, Reprod Biomed Online source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The odds of finding follicles in patients with a structural X chromosome aberration or a 45,X/47,XXX karyotype is 23%-44%, and with a 45,X karyotype 4%-11%.

    “The odds of finding follicles in patients with a structural X chromosome aberration or a 45,X/47,XXX karyotype is 23%-44% and with a 45, X karyotype 4%-11%.263,579,582”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [579] Mamsen, 2019, Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation, Fertil Steril source

      Not checked in the free run.

    • cites [582] Nadesapillai, 2023, TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Follicles were found in 58%-86% of girls with spontaneous thelarche, 62%-86% with spontaneous menarche, and in 10% without spontaneous onset of puberty.

    “Follicles were found in 58%-86% of girls with spontaneous thelarche, 62%-86% with spontaneous menarche, and in 10% without spontaneous onset of puberty.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    There are unique barriers to utilizing fertility preservation procedures for children and adolescents with TS, including the relative dearth of physicians with expertise in pediatric fertility care, the difficulty of assessing future family building goals for younger patients, and concerns about pre-adolescent/adolescent patients' ability to tolerate interventions such as ovarian stimulation or oo

    “For pediatric clinicians, reducing harm includes acknowledging unique barriers to utilizing fertility preservation procedures for children and adolescents. These include: the relative dearth of physicians with expertise in pediatric fertility care; the difficulty of assessing future family building goals for younger patients; and concerns about pre-adolescent/adolescent patients’ ability to”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [572] van der Coelen, 2022, The decision-making process regarding ovarian tissue cryopreservation in girls with Turner syndrome by patients, parents, and healthcare providers: a mixed-methods study, Horm Res Paediatr source

      Not checked in the free run.

    • cites [624] Theroux, 2022, Fertility counseling practices for patients with Turner syndrome in pediatric endocrine clinics: results of a Pediatric Endocrine Society Survey, Horm Res Paediatr source

      Not checked in the free run.

    • cites [625] Morgan, 2019, Fertility counseling and preservation discussions for females with Turner syndrome in pediatric centers: practice patterns and predictors, Fertil Steril source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Borgström et al. performed laparoscopic ovarian biopsies in 57 patients; in 15/57 girls (26%) follicles were observed.

    “Borgström et al. performed laparoscopic ovarian biopsies in 57 patients; in 15/57 girls (26%) follicles were observed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In vitro studies in mosaic girls showed most oocytes had a normal X chromosomal content, while granulosa and ovarian stromal cells were mainly aneuploid.

    “However, in vitro studies in mosaic girls have been encouraging. They showed that most oocytes had a normal X chromosomal content, while granulosa and ovarian stromal cells were mainly aneuploid.575,600,608-610”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [575] Schleedoorn, 2022, Why Turner patients with 45, X monosomy should not be excluded from fertility preservation services, Reprod Biol Endocrinol source

      Not checked in the free run.

    • cites [600] Balen, 2010, Conservation of fertility and oocyte genetics in a young woman with mosaic Turner syndrome, BJOG source

      Not checked in the free run.

    • cites [608] Nadesapillai, 2021, The challenge of defining predictive parameters for fertility preservation counseling in young females with Turner syndrome, Acta Obstet Gynecol Scand source

      Not checked in the free run.

    • cites [609] Peek, 2023, Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model, Fertil Steril source

      Not checked in the free run.

    • cites [610] Peek, 2019, Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells, Hum Reprod source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    Fertility preservation/treatment may or may not be covered by health insurance or government-funded healthcare, which may mean that these services are prohibitively expensive to patients and families with limited financial resources.

    “Fertility preservation/treatment may or may not be covered by health insurance or government-funded healthcare, which may mean that these services are prohibitively expensive to patients and families with limited financial resources.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Expectant parents are faced with many unknowns when they receive prenatal genetic counseling about TS.

    “Expectant parents are faced with many unknowns when they receive prenatal genetic counseling about TS.84”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Riggan, 2021, Prenatal genetic diagnosis of a sex chromosome aneuploidy: parent experiences, J Genet Couns source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Karyotypes 45,X, 45,X/46,iso(X), and ring X appear to be at the highest risk for ear and hearing diagnoses, however the incidence rate for ear and hearing diagnoses is 35-fold higher in all TS karyotypes combined compared to the general population.

    “Karyotypes 45,X, 45,X/46,iso(X), and ring X appear to be at the highest risk, however the incidence rate for ear and hearing diagnoses is 35-fold higher in all TS karyotypes combined compared to the general population.630,647”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

    • cites [647] Viuff, 2021, Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study, Eur J Hum Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    TS may be associated with a higher infant mortality, with studies reporting 10-16 times greater mortality in infants with TS compared to the general population.

    “However, TS may be associated with a higher infant mortality, with studies reporting 10-16 times greater mortality infants with TS compared to the general population.401,632”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [401] Dotters-Katz, 2016, The effects of Turner syndrome, 45,X on obstetric and neonatal outcomes: a retrospective cohort evaluation, Am J Perinatol source

      Not checked in the free run.

    • cites [632] Andersen, 2023, The burden of disease for children born alive with Turner syndrome-a European cohort study, Birth Defects Res source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Rates of prematurity (birth <37 weeks' gestation) in TS are similar or only slightly higher than the general population (10%-19%), with extreme prematurity uncommon.

    “Rates of prematurity (birth <37 weeks’ gestation) are similar or only slightly higher than the general population (10%-19%), with extreme prematurity uncommon.401,630,631”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [401] Dotters-Katz, 2016, The effects of Turner syndrome, 45,X on obstetric and neonatal outcomes: a retrospective cohort evaluation, Am J Perinatol source

      Not checked in the free run.

    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

    • cites [631] Sari, 2016, Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome, Am J Med Genet A source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Ptosis is noted in 2%-21%, epicanthal folds in 2%-35%, and congenital nystagmus in 2%-9% of individuals with TS.

    “Ptosis is noted in 2%-21%, epicanthal folds in 2%-35%, and congenital nystagmus in 2%-9%.644-646”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [644] Denniston, 2004, Ophthalmic features of Turner's syndrome, Eye source

      Not checked in the free run.

    • cites [645] Huang, 2022, Ocular findings in pediatric Turner syndrome, Ophthalmic Genet source

      Not checked in the free run.

    • cites [646] Wikiera, 2015, The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Approximately one-third of infants with TS are born small for gestational age (SGA), though the degree of SGA is typically mild, but can be up to 600-1000 g lighter.

    “Approximately one-third of infants with TS are born small for gestational age (SGA), though the degree of SGA is typically mild,630,631 but can be up to 600-1000 g lighter.59”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

    • cites [631] Sari, 2016, Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome, Am J Med Genet A source

      Not checked in the free run.

    • cites [59] Viuff, 2015, Only a minority of sex chromosome abnormalities are detected by the Danish national prenatal screening program for Down syndrome, Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Patients with TS interested in utilizing autologous oocytes have an apparent increased risk of pregnancy loss or birth defects and of X chromosome abnormalities being transmitted to the fetus.

    “Patients interested in utilizing autologous oocytes should be counseled on the apparent increased risk of pregnancy loss or birth defects and of X chromosome abnormalities being transmitted to the fetus.627”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [627] Oktay, 2016, Fertility preservation in women with Turner syndrome: a comprehensive review and practical guidelines, J Pediatr Adolesc Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Hearing loss affects 36%-84% of individuals with TS and negatively affects QoL and well-being.

    “Hearing loss affects 36%-84% of individuals with TS and negatively affects QoL and well-being.261,648,649”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [261] Krantz, 2019, Health-related quality of life in Turner syndrome and the influence of growth hormone therapy: a 20-year follow-up, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [648] Geerardyn, 2021, Prevalence of otological disease in Turner syndrome: a systematic review, Otol Neurotol source

      Not checked in the free run.

    • cites [649] Mann, 2024, The impact of amplification on quality of life in women with Turner syndrome, Orphanet J Rare Dis source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    An association between TS and hyperinsulinemic hypoglycemia has emerged, postulated to be due to haploinsufficiency of the gene KDM6A.

    “Recently, an association between TS and hyperinsulinemic hypoglycemia has emerged,638-642 postulated to be due to haploinsufficiency of the gene KDM6A.641”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [638] Alkhayyat, 2006, Mosaic Turner syndrome and hyperinsulinaemic hypoglycaemia, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [639] Cappella, 2015, Hyperinsulinemic hypoglycaemia in a Turner syndrome with Ring (X), Case Rep Pediatr

      Not checked in the free run.

    • cites [640] Pietzner, 2014, Low-level hyperinsulinism with hypoglycemic spells in an infant with mosaic Turner syndrome and mild kabuki-like phenotype: a case report and review of the literature, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [641] Gibson, 2018, Congenital hyperinsulinism in infants with Turner syndrome: possible association with monosomy X and KDM6A haploinsufficiency, Horm Res Paediatr source

      Not checked in the free run.

    • cites [642] Kostopoulou, 2021, Syndromic forms of hyperinsulinaemic hypoglycaemia—A 15-year follow-up study, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    Color blindness has previously been reported to be similar to the prevalence in males (8%) in TS, however a more recent study found colorblindness in only 1% of all individuals with TS.

    “Color blindness has previously been reported to be similar to the prevalence in males (8%),644 however a more recent study found colorblindness in only 1% of all individuals with TS.645”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [644] Denniston, 2004, Ophthalmic features of Turner's syndrome, Eye source

      Not checked in the free run.

    • cites [645] Huang, 2022, Ocular findings in pediatric Turner syndrome, Ophthalmic Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In approximately half of the reported cases of hyperinsulinemic hypoglycemia in TS, low blood glucose first presented within the first 24 hours of life; however, the diagnosis was made as late as one year of age.

    “In approximately half of the reported cases of hyperinsulinemic hypoglycemia, low blood glucose first presented within the first 24 hours of life; however, the diagnosis was made as late as one year of age.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Refractive errors such as hyperopia, myopia, and astigmatism affect ∼40% of individuals with TS.

    “Strabismus occurs in up to 25% of individuals with TS, and refractive errors such as hyperopia, myopia, and astigmatism affect ∼40%.644-647”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [644] Denniston, 2004, Ophthalmic features of Turner's syndrome, Eye source

      Not checked in the free run.

    • cites [645] Huang, 2022, Ocular findings in pediatric Turner syndrome, Ophthalmic Genet source

      Not checked in the free run.

    • cites [646] Wikiera, 2015, The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [647] Viuff, 2021, Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study, Eur J Hum Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Craniofacial abnormalities, history of middle ear disease, aortic anomalies, metabolic syndrome, and age have all been associated with hearing loss severity and progression in TS.

    “Craniofacial abnormalities, history of middle ear disease, aortic anomalies, metabolic syndrome, and age have all been associated with hearing loss severity and progression in TS.647,650,653”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [647] Viuff, 2021, Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study, Eur J Hum Genet source

      Not checked in the free run.

    • cites [650] Hamberis, 2020, Characteristics and progression of hearing loss in children with Turner's syndrome, Laryngoscope source

      Not checked in the free run.

    • cites [653] Álvarez-Nava, 2020, Metabolic syndrome as a risk factor for sensorineural hearing loss in adult patients with Turner syndrome, Appl Clin Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Strabismus occurs in up to 25% of individuals with TS.

    “Strabismus occurs in up to 25% of individuals with TS, and refractive errors such as hyperopia, myopia, and astigmatism affect ∼40%.644-647”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [644] Denniston, 2004, Ophthalmic features of Turner's syndrome, Eye source

      Not checked in the free run.

    • cites [645] Huang, 2022, Ocular findings in pediatric Turner syndrome, Ophthalmic Genet source

      Not checked in the free run.

    • cites [646] Wikiera, 2015, The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [647] Viuff, 2021, Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study, Eur J Hum Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Several conditions may not be apparent until after birth in TS, although many complex congenital anomalies can be identified through prenatal imaging.

    “Although many complex congenital anomalies can be identified through prenatal imaging, several conditions may not be apparent until after birth.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    A mid-frequency dip is an early sign of sensorineural hearing loss in TS, followed by early onset presbycusis-like high frequency loss.

    “A mid-frequency dip is an early sign, followed by early onset presbycusis-like high frequency loss.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Dental and periodontal problems in TS include reduced tooth crown height (predominant finding), alteration in tooth morphology and root size, bifurcated and supernumerary roots, increased root resorption, increased tooth mobility, early tooth loss, smaller primary and permanent teeth, thin hypoplastic enamel, abnormal dentin, variation in eruption patterns and periodontal disease.

    “Dental and periodontal problems in TS include reduced tooth crown height (predominant finding), alteration in tooth morphology and root size, bifurcated and supernumerary roots, increased root resorption, increased tooth mobility, early tooth loss, smaller primary and permanent teeth, thin hypoplastic enamel, abnormal dentin, variation in eruption patterns and periodontal disease.663-665”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [663] Maier, 2019, Tooth crown morphology in Turner and Klinefelter syndrome individuals from a Croatian sample, Acta Stomatol Croat source

      Not checked in the free run.

    • cites [664] Preda, 2021, Histopathological and immunohistochemical changes of the marginal periodontium in patients with Turner syndrome, Rom J Morphol Embryol source

      Not checked in the free run.

    • cites [665] Kjellberg, 2022, Apical root resorptions in girls with Turner syndrome: a controlled longitudinal study, Eur J Orthod source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    While caries may be less prevalent, periodontal disease such as gingivitis appears to be more common in TS.

    “While caries may be less prevalent, periodontal disease such as gingivitis appears to be more common.664”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [664] Preda, 2021, Histopathological and immunohistochemical changes of the marginal periodontium in patients with Turner syndrome, Rom J Morphol Embryol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Underdevelopment of several facial structures, an increased cranial base angle, a small and narrow mandible, maxillary hypoplasia and retrusion, high-arched and narrowed palate, micrognathia, malocclusion, bilateral crossbite and ectopic tooth eruption have all been described in TS.

    “Underdevelopment of several facial structures, an increased cranial base angle, a small and narrow mandible, maxillary hypoplasia and retrusion, high-arched and narrowed palate, micrognathia, malocclusion, bilateral crossbite and ectopic tooth eruption have all been described.666,667”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [666] Ahiko, 2019, Investigation of maxillofacial morphology and oral characteristics with Turner syndrome and early mixed dentition, Congenit Anom (Kyoto) source

      Not checked in the free run.

    • cites [667] Cazzolla, 2018, Orthopedic-orthodontic treatment of the patient with Turner's syndrome: review of the literature and case report, Spec Care Dentist source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Webbed neck has been reported in 18%-25% of individuals with TS, and patients with webbed neck have 3.3 (1.5-7.4) times the odds of coarctation of the aorta or BAV compared to those without webbed neck.

    “Webbed neck has been reported in 18%-25% of individuals with TS,16,677 and patients with webbed neck have 3.3 (1.5-7.4) times the odds of coarctation of the aorta or BAV compared to those without webbed neck.393”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Carvalho, 2018, Clinical and cytogenetic features of 516 patients with suspected Turner syndrome—a single-center experience, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [677] Wonkam, 2015, Features of Turner syndrome among a group of Cameroonian patients, Int J Gynaecol Obstet source

      Not checked in the free run.

    • cites [393] Loscalzo, 2005, Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    While surgery may be done to correct webbed neck, there are no data to suggest superiority of one technique over another.

    “While surgery may be done to correct webbed neck, there are no data to suggest superiority of one technique over another.678”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [678] Jungbauer, 2022, Surgical techniques for the repair of webbed neck: a scoping review, J Craniofac Surg source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Potential complications of surgical corrections for webbed neck include hypertrophy of the surgical scar (keloid formation) and recurrence of the webbed neck.

    “Potential complications of surgical corrections that have been reported include hypertrophy of the surgical scar (keloid formation)678,679 and recurrence of the webbed neck.678”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [678] Jungbauer, 2022, Surgical techniques for the repair of webbed neck: a scoping review, J Craniofac Surg source

      Not checked in the free run.

    • cites [679] Mehri Turki, 2017, Surgical correction of the webbed neck: an alternative lateral approach, GMS Interdiscip Plast Reconstr Surg DGPW

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Clinically apparent lymphedema occurs in 12%-27% of girls and women with TS.

    “Clinically apparent lymphedema occurs in 12%-27% of girls and women with TS.16,88,673”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Carvalho, 2018, Clinical and cytogenetic features of 516 patients with suspected Turner syndrome—a single-center experience, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [88] Mohamed, 2015, Mode of initial presentation and chromosomal abnormalities in Irish patients with Turner syndrome: a single-centre experience, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [673] Said, 2022, Dermatologic findings in individuals with Turner syndrome: a cross-sectional study across the lifespan, J Am Acad Dermatol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Neither estrogen nor GH therapy has been associated with ear disease or hearing loss in TS.

    “Neither estrogen nor GH therapy has been associated with ear disease or hearing loss in TS.647,652,660”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [647] Viuff, 2021, Disorders of the eye, ear, skin, and nervous system in women with Turner syndrome -a nationwide cohort study, Eur J Hum Genet source

      Not checked in the free run.

    • cites [652] Kubba, 2019, Annual hearing screening in girls with Turner syndrome: results from the first three years in Glasgow, Int J Pediatr Otorhinolaryngol source

      Not checked in the free run.

    • cites [660] Ostberg, 2004, Oestrogen deficiency and growth hormone treatment in childhood are not associated with hearing in adults with Turner syndrome, Horm Res

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Clinical lymphedema is often present at birth, frequently resolves or at least improves by age 2 years, and may have a relapsing and remitting course throughout life.

    “Clinical lymphedema is often present at birth, frequently resolves or at least improves by age 2 years, and may have a relapsing and remitting course throughout life.675”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [675] Atton, 2015, The lymphatic phenotype in Turner syndrome: an evaluation of nineteen patients and literature review, Eur J Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    Currently, there are no recommended surgical or pharmaceutical therapies for treatment of lymphedema in the context of TS.

    “Currently, there are no recommended surgical or pharmaceutical therapies for treatment of lymphedema in the context of TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Fetal lymphedema may present as cystic hygroma and hydrops fetalis; both conditions conferring an increased risk for spontaneous fetal demise.

    “Fetal lymphedema may present as cystic hygroma and hydrops fetalis; both conditions conferring an increased risk for spontaneous fetal demise.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Sensorineural hearing loss affects around one third of all individuals with TS and can occur even in the absence of preexisting middle ear pathology.

    “Sensorineural hearing loss affects around one third of all individuals with TS and can occur even in the absence of preexisting middle ear pathology.651”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [651] Bonnard, 2019, Clinical update on sensorineural hearing loss in Turner syndrome and the X-chromosome, Am J Med Genet C Semin Med Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Progression to severe hearing loss is less common but does occur in TS, in which case rehabilitation with cochlear implantation may be necessary.

    “Progression to severe hearing loss is less common but does occur, in which case rehabilitation with cochlear implantation may be necessary.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    GH treatment has been shown to have a positive impact on craniofacial dimensions; however it does not correct the proportional and positional anomalies in TS.

    “GH treatment has been shown to have a positive impact on craniofacial dimensions; however it does not correct the proportional and positional anomalies in TS.668”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [668] Wójcik, 2020, Craniofacial morphology in children with growth hormone deficiency and Turner syndrome, Diagnostics (Basel) source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    The prevalence of sensorineural hearing loss in TS increases with age, however children can also be affected.

    “The prevalence of sensorineural hearing loss in TS increases with age, however children can also be affected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Horseshoe kidney and duplicated collecting system are the most common findings in TS, each occurring at a frequency of 15%-20%.

    “Horseshoe kidney and duplicated collecting system are the most common findings in TS, each occurring at a frequency of 15%-20%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Youth with TS have higher waist circumference and visceral adiposity.

    “Youth with TS have higher waist circumference and visceral adiposity.477”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [477] O’Gorman, 2013, An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Other dermatological problems more often noted in girls and women with TS include keloid scarring, vitiligo, alopecia areata, and lichen sclerosis, though additional data are needed to determine the association between these conditions and TS.

    “Other dermatological problems more often noted in girls and women with TS include keloid scarring, vitiligo, alopecia areata, and lichen sclerosis, though additional data are needed to determine the association between these conditions and TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    A quarter of children and half of young adults with TS have dyslipidemia and hyperlipidemia is present in about 30% of adults and is closely linked with BMI.

    “A quarter of children and half of young adults with TS have dyslipidemia450,696,697 and hyperlipidemia is present in about 30% of adults and is closely linked with BMI.331”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [450] Lebenthal, 2018, The natural history of metabolic comorbidities in Turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [696] Kelley, 2017, Increased non-high-density lipoprotein cholesterol in children and young adults with Turner syndrome is not explained by BMI alone, Horm Res Paediatr source

      Not checked in the free run.

    • cites [697] Malhotra, 2023, Isochromosome Xq and the risk of metabolic comorbidities in Turner syndrome, Diabetes Metab Syndr source

      Not checked in the free run.

    • cites [331] Sandahl, 2023, A prospective study of lipids in adult women with Turner syndrome, J Endocr Soc source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    One pediatric study of 122 children with TS up to age 18 years showed normal estimated glomerular filtration rate (eGFR) over time, though there was a small decline in four girls.

    “One pediatric study of 122 children with TS up to age 18 years showed normal estimated glomerular filtration rate (eGFR) over time, though there was a small decline in four girls.691”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [691] Izumita, 2020, Retrospective study of the renal function using estimated glomerular filtration rate and congenital anomalies of the kidney-urinary tract in pediatric Turner syndrome, Congenit Anom (Kyoto) source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    To date, there are no data directly linking cholesterol profiles to morbidity or mortality in TS, and there are no studies evaluating treatment of dyslipidemia in TS.

    “To date, there are no data directly linking cholesterol profiles to morbidity or mortality in TS, and there are no studies evaluating treatment of dyslipidemia in TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Both visceral and total fat mass are elevated in adults with TS, while lean body mass and skeletal muscle mass are decreased.

    “Both visceral and total fat mass are elevated in adults with TS, while lean body mass and skeletal muscle mass are decreased.701”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [701] Gravholt, 2006, Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules, Eur J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Resting energy expenditure (REE) does not seem to explain the difference in overweight/obesity in TS as resting energy expenditure per fat-free mass is actually higher in girls with TS, and a study in adults found higher body fat, lower leptin concentrations, and no difference in resting energy expenditure per fat-free mass compared to controls.

    “Resting energy expenditure (REE) does not seem to explain the difference as resting energy expenditure per fat-free mass is actually higher in girls with TS,699 and a study in adults found higher body fat, lower leptin concentrations, and no difference in resting energy expenditure per fat-free mass compared to controls.700”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [699] Binder, 2017, Resting energy expenditure in girls with Turner syndrome, J Pediatr Endocrinol Metab source

      Not checked in the free run.

    • cites [700] Gravholt, 2000, Lp(a) and lipids in adult Turner's syndrome: impact of treatment with 17beta-estradiol and norethisterone, Atherosclerosis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Individuals with TS have a prevalence of overweight/obesity as high as 48% with some variation due to small samples sizes, age, definitions, and local prevalence of overweight/obesity.

    “Individuals with TS have a prevalence of overweight/obesity as high as 48% with some variation due to small samples sizes, age, definitions, and local prevalence of overweight/obesity.450,693-697”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [450] Lebenthal, 2018, The natural history of metabolic comorbidities in Turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [693] Álvarez-Nava, 2019, Anthropometric variables as cardiovascular risk predictors in a cohort of adult subjects with Turner syndrome, Diabetes Metab Syndr Obes source

      Not checked in the free run.

    • cites [694] Salem, 2021, Epicardial and perihepatic fat as cardiometabolic risk predictors in girls with Turner syndrome: a cardiac magnetic resonance study, J Clin Res Pediatr Endocrinol source

      Not checked in the free run.

    • cites [695] Hanew, 2016, Women with Turner syndrome are at high risk of lifestyle-related disease -from questionnaire surveys by the Foundation for Growth Science in Japan, Endocr J source

      Not checked in the free run.

    • cites [696] Kelley, 2017, Increased non-high-density lipoprotein cholesterol in children and young adults with Turner syndrome is not explained by BMI alone, Horm Res Paediatr source

      Not checked in the free run.

    • cites [697] Malhotra, 2023, Isochromosome Xq and the risk of metabolic comorbidities in Turner syndrome, Diabetes Metab Syndr source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Ultrasound yields low sensitivity for identifying duplex kidneys and axis/rotational differences, whereas bowel gas may obscure horseshoe kidney.

    “Ultrasound yields low sensitivity for identifying duplex kidneys and axis/rotational differences, whereas bowel gas may obscure horseshoe kidney.692”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [692] Chang, 2000, Renal malformations in children with Turner's syndrome, J Formos Med Assoc

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Although the majority of diabetes in adult women with TS is attributed to type 2 diabetes, there is accumulating data for a TS-specific type of diabetes.

    “Although the majority of diabetes in adult women is attributed to type 2 diabetes,384 there is accumulating data for a TS-specific type of diabetes.384,707”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [707] Álvarez-Nava, 2020, Insulin sensitivity and pancreatic β-cell function in Ecuadorian women with Turner syndrome, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Individuals with TS are at an increased risk for both type 1 and type 2 diabetes.

    “Individuals with TS are at an increased risk for both type 1 and type 2 diabetes.29,222,227,357,384,706”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [29] Viuff, 2020, Sex hormone replacement therapy in Turner syndrome—impact on morbidity and mortality, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [222] Bolar, 2008, Long-term safety of recombinant human growth hormone in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [227] Bakalov, 2004, Impaired insulin secretion in the Turner metabolic syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [357] Gravholt, 1998, Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement, Diabetes Care source

      Not checked in the free run.

    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [706] Jorgensen, 2010, Autoimmune diseases in women with Turner's syndrome, Arthritis Rheum source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Despite a wide range of abnormal renal morphology, long-term kidney function remains normal in most youth and young adults with TS, although there are few longitudinal studies.

    “In contrast, despite a wide range of abnormal renal morphology, long-term kidney function remains normal in most youth and young adults with TS,17,27,690 although there are few longitudinal studies.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Gravholt, 2023, The changing face of Turner syndrome, Endocr Rev source

      Not checked in the free run.

    • cites [27] Schoemaker, 2008, Mortality in women with Turner syndrome in Great Britain: a national cohort study, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [690] Pasquali, 2009, Collectrin gene screening in Turner syndrome patients with kidney malformation, J Genet source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The 45,X karyotype is associated with increased risk for benign skin neoplasms [HR 2.03 (1.42-2.9)] and non-melanomatous skin cancer [HR 5.38 (2.63-10.98)].

    “The 45,X karyotype is associated with increased risk for benign skin neoplasms [HR 2.03 (1.42-2.9)] and non-melanomatous skin cancer [HR 5.38 (2.63-10.98)].332”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [332] Viuff, 2021, Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy, Eur J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Other associated conditions include malrotation or positional rotation of the kidneys (5%), single kidney (<5%), and multi-cystic kidneys (<5%).

    “Other associated conditions include malrotation or positional rotation of the kidneys (5%), single kidney (<5%), and multi-cystic kidneys (<5%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Overweight/obesity increases from childhood to adulthood in TS, with a cumulative incidence of 8%-60% from age 10 to 30 years.

    “Overweight/obesity increases from childhood to adulthood, with a cumulative incidence of 8%-60% from age 10 to 30 years.630”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Diabetes mellitus is common in TS, with studies reporting a 25%-70% lifetime prevalence.

    “Diabetes mellitus is common in TS, with studies reporting a 25%-70% lifetime prevalence.703-705”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [703] Bakalov, 2009, X-chromosome gene dosage and the risk of diabetes in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [704] Ibarra-Gasparini, 2018, New insights on diabetes in Turner syndrome: results from an observational study in adulthood, Endocrine source

      Not checked in the free run.

    • cites [705] Sun, 2019, Glucose metabolism in Turner syndrome, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Factors related to the increase in overweight/obesity in TS have not been well elucidated, though fetal programming and small for gestational age (SGA) have been proposed as contributing factors.

    “Factors related to the increase in overweight/obesity have not been well elucidated, though fetal programming and small for gestational age (SGA) have been proposed as contributing factors.698”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [698] Baldin, 2011, Turner syndrome and metabolic derangements: another example of fetal programming, Early Hum Dev source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    A specific mechanism underlying the immune dysfunction in TS leading to these skin conditions has not been elucidated.

    “A specific mechanism underlying the immune dysfunction in TS leading to these skin conditions has not been elucidated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Age, BMI, and waist-to-height ratio correlate with adverse lipid profiles but account for only a minority of the variability in TS.

    “Age, BMI, and waist-to-height ratio correlate with adverse lipid profiles but account for only a minority of the variability.693,696”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [693] Álvarez-Nava, 2019, Anthropometric variables as cardiovascular risk predictors in a cohort of adult subjects with Turner syndrome, Diabetes Metab Syndr Obes source

      Not checked in the free run.

    • cites [696] Kelley, 2017, Increased non-high-density lipoprotein cholesterol in children and young adults with Turner syndrome is not explained by BMI alone, Horm Res Paediatr source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Multiple studies demonstrate impaired beta cell function as well as reduced insulin sensitivity are involved in the development of diabetes in TS, while one study found glucose intolerance despite apparently normal beta cell function.

    “Furthermore, multiple studies demonstrate impaired beta cell function as well as reduced insulin sensitivity are involved in the development of diabetes in TS ,227,229,384,705,707,708 while one study found glucose intolerance despite apparently normal beta cell function.709”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [227] Bakalov, 2004, Impaired insulin secretion in the Turner metabolic syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [229] Baronio, 2017, The influence of GH treatment on glucose homeostasis in girls with Turner syndrome: a 7-year study, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [705] Sun, 2019, Glucose metabolism in Turner syndrome, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [707] Álvarez-Nava, 2020, Insulin sensitivity and pancreatic β-cell function in Ecuadorian women with Turner syndrome, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [708] Sheanon, 2021, Increased prevalence of β-cell dysfunction despite normal HbA1c in youth and young adults with Turner syndrome, Horm Res Paediatr source

      Not checked in the free run.

    • cites [709] Hjerrild, 2011, Delayed beta-cell response and glucose intolerance in young women with Turner syndrome, BMC Endocr Disord source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    There is also evidence that GH is not associated with an increased risk of diabetes in TS and better heart health in TS.

    “There is also evidence that GH is not associated with an increased risk of diabetes in TS229,384 and better heart health713 in TS.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [229] Baronio, 2017, The influence of GH treatment on glucose homeostasis in girls with Turner syndrome: a 7-year study, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [713] Dyrka, 2020, The influence of growth hormone therapy on the cardiovascular system in Turner syndrome, J Pediatr Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The available literature shows that girls and women with TS do not meet current general recommendations for physical activity, which is concerning because less physical activity has been associated with excess weight gain and hypertension in adults with TS.

    “The available literature shows that girls and women with TS do not meet current general recommendations for physical activity,357,455,496-498 which is concerning because less physical activity has been associated with excess weight gain and hypertension in adults with TS.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [357] Gravholt, 1998, Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement, Diabetes Care source

      Not checked in the free run.

    • cites [455] Landin-Wilhelmsen, 2001, Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [496] Santi, 2021, Health behaviour of women with Turner syndrome, Acta Paediatr source

      Not checked in the free run.

    • cites [497] Thompson, 2020, A mixed methods study of physical activity and quality of life in adolescents with Turner syndrome, Am J Med Genet A source

      Not checked in the free run.

    • cites [498] Arnold, 2021, Physical activity and diet quality: effects on cardiovascular morbidity in women with Turner syndrome-results from an online patient survey, J Clin Med source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Some studies have found an association of metabolic abnormalities with monosomy X, ring X, isochromosome Xq, and Xp deletion, however findings are inconsistent and require more data before clinical interpretation.

    “Some studies have found an association of metabolic abnormalities with monosomy X, ring X, isochromosome Xq, and Xp deletion, however findings are inconsistent and require more data before clinical interpretation.450,630,697,703”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [450] Lebenthal, 2018, The natural history of metabolic comorbidities in Turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

    • cites [697] Malhotra, 2023, Isochromosome Xq and the risk of metabolic comorbidities in Turner syndrome, Diabetes Metab Syndr source

      Not checked in the free run.

    • cites [703] Bakalov, 2009, X-chromosome gene dosage and the risk of diabetes in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    BMI increases during the time that girls with TS are on GH therapy, although body composition in adults who had been treated with GH was not different from those who did not receive GH.

    “BMI increases during the time that girls with TS are on GH therapy,379 although body composition in adults who had been treated with GH was not different from those who did not receive GH.711”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [379] Reinehr, 2016, Weight gain in Turner syndrome: association to puberty induction?—longitudinal analysis of KIGS data, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [711] Baldin, 2010, Effects of growth hormone on body proportions in Turner syndrome compared with non-treated patients and normal women, J Endocrinol Invest source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Another study found only 37% of TS adults had received nutrition counseling and only one fifth of these were adherent to the recommended Mediterranean diet which is believed to support cardiometabolic health.

    “Another study found only 37% of TS adults had received nutrition counseling and only one fifth of these were adherent to the recommended Mediterranean diet which is believed to support cardiometabolic health.498”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [498] Arnold, 2021, Physical activity and diet quality: effects on cardiovascular morbidity in women with Turner syndrome-results from an online patient survey, J Clin Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    There is no information available on use of pharmacotherapy for the treatment of obesity in TS.

    “There is no information available on use of pharmacotherapy for the treatment of obesity in TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Several studies support that diabetes occurs at an earlier age and is less likely to involve the usual risk factors (BMI, body composition, and family history) in TS compared to the general population.

    “Several studies support that diabetes occurs at an earlier age384,708 and is less likely to involve the usual risk factors (BMI, body composition, and family history) in TS compared to the general population.704”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [708] Sheanon, 2021, Increased prevalence of β-cell dysfunction despite normal HbA1c in youth and young adults with Turner syndrome, Horm Res Paediatr source

      Not checked in the free run.

    • cites [704] Ibarra-Gasparini, 2018, New insights on diabetes in Turner syndrome: results from an observational study in adulthood, Endocrine source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    GH increases insulin resistance; however, estrogen replacement appears to reverse this and the insulin resistance reverses after completion of GH therapy.

    “GH increases insulin resistance; however, estrogen replacement appears to reverse this712 and the insulin resistance reverses after completion of GH therapy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [712] Segerer, 2020, Increased insulin concentrations during growth hormone treatment in girls with Turner syndrome are ameliorated by hormone replacement therapy, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    These advances cover all specialty fields involved in the care of girls and women with TS.

    “These advances cover all specialty fields involved in the care of girls and women with TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Other ultrasound findings suggestive of TS include left-sided cardiac anomalies, partial anomalous pulmonary venous return/connection and persistent left superior vena cava, renal anomalies, small omphalocele, short femur and fetal growth restriction.

    “Other ultrasound findings suggestive of TS include left-sided cardiac anomalies, partial anomalous pulmonary venous return/connection and persistent left superior vena cava, renal anomalies, small omphalocele, short femur and fetal growth restriction.45,50-54”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [45] Bronshtein, 2003, A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy, Am J Obstet Gynecol source

      Not checked in the free run.

    • cites [50] Surerus, 2003, Turner's syndrome in fetal life, Ultrasound Obstet Gynecol source

      Not checked in the free run.

    • cites [51] Bedei, 2023, Turner syndrome-omphalocele association: incidence, karyotype, phenotype and fetal outcome, Prenat Diagn source

      Not checked in the free run.

    • cites [52] Wagner, 2016, First-trimester screening for trisomies 18 and 13, triploidy and Turner syndrome by detailed early anomaly scan, Ultrasound Obstet Gynecol source

      Not checked in the free run.

    • cites [53] Baena, 2004, Turner syndrome: evaluation of prenatal diagnosis in 19 European registries, Am J Med Genet source

      Not checked in the free run.

    • cites [54] Kagan, 2010, The 11–13-week scan: diagnosis and outcome of holoprosencephaly, exomphalos and megacystis, Ultrasound Obstet Gynecol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    45,X/46,XY mosaicism and its variants have an estimated prevalence of 3-15 per 100 000 newborns, with new data showing a prevalence of 5.6 per 100 000 liveborn phenotypically male infants and 2.1 per 100 000 liveborn phenotypically female infants.

    “45,X/46,XY mosaicism and its variants (45,X/47,XXY, structural abnormalities of the Y chromosome) have an estimated prevalence of 3-15 per 100 000 newborns,37,38 with new data showing a prevalence of 5.6 per 100 000 liveborn phenotypically male infants and 2.1 per 100 000 liveborn phenotypically female infants.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Hamerton, 1975, A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities, Clin Genet source

      Not checked in the free run.

    • cites [38] Nielsen, 1991, Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark, Hum Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All other recommendations were derived from majority consensus of the guideline development working group.

    “All other recommendations were derived from majority consensus of the guideline development working group, but, if members had substantive disagreements, this is acknowledged in the manuscript.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Microarray can provide better resolution compared to karyotyping, but has limitations in detecting low level 45,X mosaicism (<10%, though studies show detection as low as 5%), and in interpreting structural variants.

    “Microarray can provide better resolution compared to karyotyping, but has limitations in detecting low level 45,X mosaicism (<10%, though studies show detection as low as 5%),20 and in interpreting structural variants (ie, mosaic isodicentric Xp chromosome).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Prakash, 2014, Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome, Genet Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the first trimester, markedly increased nuchal translucency is common in fetuses with TS, but is also observed in other genetic conditions, especially chromosome abnormality syndromes and RASopathies, or with fetal structural anomalies.

    “In the first trimester, markedly increased nuchal translucency (especially in cases of associated cardiac anomalies) is common in fetuses with TS, but is also observed in other genetic conditions, especially chromosome abnormality syndromes and RASopathies, or with fetal structural anomalies.46-50”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [46] Kagan, 2006, Relation between increased fetal nuchal translucency thickness and chromosomal defects, Obstet Gynecol source

      Not checked in the free run.

    • cites [47] Pauta, 2022, Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency: systematic review and meta-analysis, Ultrasound Obstet Gynecol source

      Not checked in the free run.

    • cites [48] Stuurman, 2019, Prenatal ultrasound findings of rasopathies in a cohort of 424 fetuses: update on genetic testing in the NGS era, J Med Genet source

      Not checked in the free run.

    • cites [49] Bardi, 2020, Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?, Prenat Diagn source

      Not checked in the free run.

    • cites [50] Surerus, 2003, Turner's syndrome in fetal life, Ultrasound Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS and a 45,X/46,XX mosaic karyotype present with a milder phenotype with left-sided congenital heart defects, obesity and hypertension being less frequent, age at menarche being near-normal and are more likely to experience spontaneous menarche and pregnancies compared to individuals with TS and 45,X.

    “In general, individuals with TS and a 45,X/46,XX mosaic karyotype present with a milder phenotype with left-sided congenital heart defects, obesity and hypertension being less frequent, age at menarche being near-normal and are more likely to experience spontaneous menarche and pregnancies compared to individuals with TS and 45,X.26,30”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [30] Noordman, 2019, Karyotype—phenotype associations in patients with Turner syndrome, Pediatr Endocrinol Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TS individuals with a ring X chromosome without functional loss of XIST seem to have an increased risk of metabolic syndrome compared with TS individuals with 45,X but appear to have the lowest risk of BAV.

    “TS individuals with a ring X chromosome without functional loss of XIST seem to have an increased risk of metabolic syndrome compared with TS individuals with 45,X but in contrast, they appear to have the lowest risk of BAV.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS and a 45,X karyotype have a significantly higher frequency of comorbidities and a higher mortality compared to individuals with other TS karyotypes.

    “Overall, individuals with TS and a 45,X karyotype have a significantly higher frequency of comorbidities and a higher mortality compared to individuals with other TS karyotypes.25-29”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [25] Schoemaker, 2008, Cancer incidence in women with Turner syndrome in Britain: a national cohort study, Lancet Oncol source

      Not checked in the free run.

    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [27] Schoemaker, 2008, Mortality in women with Turner syndrome in Great Britain: a national cohort study, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [28] Stochholm, 2006, Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [29] Viuff, 2020, Sex hormone replacement therapy in Turner syndrome—impact on morbidity and mortality, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Diagnosis of 45,X/46,XY mosaicism is delayed to a median age of 29 years in male individuals and 13 years in female individuals, and these karyotypes are associated with elevated morbidity and mortality.

    “Diagnosis is delayed to a median age of 29 years (male individuals) and 13 years (female individuals),39 and these karyotypes are associated with various phenotypes, accompanied by elevated morbidity40 and mortality.39”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [39] Stochholm, 2024, Incidence, prevalence, age at diagnosis, and mortality in individuals with 45,X/46,XY mosaicism: a population-based registry study, Genet Med source

      Not checked in the free run.

    • cites [40] Alkhunaizi, 2024, 45,X/46,XY mosaicism: clinical manifestations and long term follow-up, Am J Med Genet A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All participants completed conflict-of-interest forms.

    “All participants completed conflict-of-interest forms (Appendix S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Individuals with TS and 45,X/47,XXX karyotype have a milder external and cardiovascular phenotype compared to 45,X, but neurodevelopmental disabilities and mental health domains remain a concern.

    “In general, individuals with TS and 45,X/47,XXX karyotype also have a milder external and cardiovascular phenotype compared to 45,X, but neurodevelopmental disabilities and mental health domains remain a concern.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Sybert, 2002, Phenotypic effects of mosaicism for a 47,XXX cell line in Turner syndrome, J Med Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A draft of the guideline was submitted for external review and commentary with/without endorsement by the professional societies.

    “A draft of the guideline was submitted for external review and commentary with/without endorsement by the professional societies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In women less than 50 years of age, there has been no specific lower limit for 45,X that defines TS, although many have used 5%.

    “In women less than 50 years of age, there has been no specific lower limit for 45,X that defines TS, although many have used 5%.11,12”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [12] El-Mansoury, 2007, Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The guidelines used GRADE as a methodological base for four clinical questions.

    “In short, the guidelines used GRADE as a methodological base for four clinical questions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Individuals with TS and 45,X/46,XY seem to have the lowest incidence of autoimmune thyroid disease and severe hearing loss and a low incidence of aortic coarctation.

    “Individuals with TS and with 45,X/46,XY seem to have the lowest incidence of autoimmune thyroid disease and severe hearing loss and a low incidence of aortic coarctation.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It has not been determined whether there is a cut-off point of the percentage of 45,X below which surveillance does not apply.

    “In addition, it has not been determined whether there is a “cut-off” point of the percentage of 45,X below which surveillance does not apply.13”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Snyder, 2021, Genetic counseling for women with 45,X/46,XX mosaicism: towards more personalized management, Eur J Med Genet source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Most TS individuals will need HRT-first for induction of puberty and later for maintaining secondary sex characteristics, attaining peak bone mass, normalizing uterine growth.

    “Most TS individuals will therefore need HRT—first for induction of puberty and later for maintaining secondary sex characteristics, attaining peak bone mass, normalizing uterine growth (for possible pregnancy later).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All comments and suggestions were discussed and implemented as appropriate by the working/writing group.

    “All comments and suggestions were discussed and implemented as appropriate by the working/writing group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Abnormalities in fetuses with TS can be present already in the first trimester and may regress with advancing gestational age.

    “Abnormalities can be present already in the first trimester and may regress with advancing gestational age.45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Bronshtein, 2003, A characteristic cluster of fetal sonographic markers that are predictive of fetal Turner syndrome in early pregnancy, Am J Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS and isochromosome Xq present with an intermediate phenotype regarding left-sided congenital heart defects and spontaneous menarche, and seem to have a lower incidence of aortic coarctation.

    “Overall, individuals with TS and isochromosome Xq present with an intermediate phenotype regarding left-sided congenital heart defects and spontaneous menarche, and also seem to have a lower incidence of aortic coarctation.26,30”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [30] Noordman, 2019, Karyotype—phenotype associations in patients with Turner syndrome, Pediatr Endocrinol Rev

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Formal evidence syntheses were performed and graded only for the four GRADE questions.

    “Formal evidence syntheses were performed and graded only for these questions.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    When girls with TS are not identified in infancy by characteristic features such as lymphedema and webbed neck, the diagnosis is often made years after growth failure ensues, and sometimes little or no growth potential remains.

    “When girls with TS are not identified in infancy by characteristic features such as lymphedema and webbed neck, the diagnosis is often made years after growth failure ensues, and sometimes little or no growth potential remains.28,85-88”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [28] Stochholm, 2006, Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [85] Savendahl, 2000, Delayed diagnoses of Turner's syndrome: proposed guidelines for change, J Pediatr source

      Not checked in the free run.

    • cites [86] Gravholt, 1996, Prenatal and postnatal prevalence of Turner's syndrome: a registry study, BMJ source

      Not checked in the free run.

    • cites [87] Lee, 2014, Turner's syndrome: challenges of late diagnosis, Lancet Diabetes Endocrinol source

      Not checked in the free run.

    • cites [88] Mohamed, 2015, Mode of initial presentation and chromosomal abnormalities in Irish patients with Turner syndrome: a single-centre experience, J Pediatr Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Pre-implantation genetic testing is currently offered to women with recurrent pregnancy loss or repetitive implantation failure after in vitro fertilization procedures although the clinical benefit is an ongoing topic of discussion.

    “Pre-implantation genetic testing is currently offered to women with recurrent pregnancy loss or repetitive implantation failure after in vitro fertilization procedures although the clinical benefit is an ongoing topic of discussion.74,75”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [74] Cornelisse, 2020, Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation, Cochrane Database Syst Rev

      Not checked in the free run.

    • cites [75] De Rycke, 2020, PREIMPLANTATION GENETIC TESTING: clinical experience of preimplantation genetic testing, Reproduction source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several factors influence prospective parents' decision to continue or terminate a pregnancy with a TS fetus, including fetal ultrasound abnormalities, incidental findings, presence or absence of mosaicism, gestational age at diagnosis, parental age, number of previous children, possibility of infertility, parents' fear/anxiety, parents' socioeconomic status and religious background, ethnicity,遗传学

    “Several factors have been found to influence the prospective parents’ decision to continue or terminate a pregnancy with a TS fetus.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [81] Jeon, 2012, Decision to abort after a prenatal diagnosis of sex chromosome abnormality: a systematic review of the literature, Genet Med source

      Not checked in the free run.

    • cites [83] Jaramillo, 2019, Delivering the diagnosis of sex chromosome aneuploidy: experiences and preferences of parents and individuals, Clin Pediatr (Phila) source

      Not checked in the free run.

    • cites [84] Riggan, 2021, Prenatal genetic diagnosis of a sex chromosome aneuploidy: parent experiences, J Genet Couns source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the United States, nomination of a condition to the Recommended Uniform Newborn Screening Panel requires a high certainty that screening would lead to significant net benefit, high-to-moderate feasibility, and ability to implement within 3 years.

    “In the United States, nomination of a condition to the Recommended Uniform Newborn Screening Panel requires a high certainty that screening for the targeted condition would lead to a significant net benefit, that screening has high-to-moderate feasibility and that most state screening programs would be able to implement screening within 3 years.95”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Kemper, 2014, Decision-making process for conditions nominated to the recommended uniform screening panel: statement of the US department of health and human services secretary's advisory committee on heritable disorders in newborns and children, Genet Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Abnormal results in prenatal serum screening may suggest TS, but these tests may be normal together with normal nuchal translucency thickness.

    “Abnormal results in prenatal serum screening (PAPP-A as part of combined first trimester screening, triple or quadruple test) even though not specifically intended to screen for TS, may also suggest this condition.59,60 However, these tests may be normal together with normal nuchal translucency thickness.59”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [59] Viuff, 2015, Only a minority of sex chromosome abnormalities are detected by the Danish national prenatal screening program for Down syndrome, Hum Reprod source

      Not checked in the free run.

    • cites [60] Maiz, 2009, Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11–13 weeks of gestation, Ultrasound Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Employing PCR of the ARSE and MAGEH1 genes, all but one patient with TS was detected (sensitivity 95%), and only 0.6% of newborns required recall for karyotypes.

    “Employing PCR of the ARSE and MAGEH1 genes, all but one patient with TS was detected (albeit only 10 patients with mosaicism were tested) for a detection sensitivity of 95%, and only 0.6% of the newborns required recall for karyotypes.90”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [90] Correa, 2014, Neonatal detection of Turner syndrome by real-time PCR gene quantification of the ARSE and MAGEH1 genes, Genet Mol Res source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Prior to considering newborn screening for TS, additional improvements in methodology and systems will be required.

    “We conclude that prior to considering newborn screening for TS, additional improvements in methodology and systems will be required.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Non-mosaic 45,X fetuses with marked cystic hygroma and/or fetal hydrops often result in miscarriage, but these findings are also compatible with delivery of a viable newborn.

    “Although non-mosaic 45,X fetuses with marked cystic hygroma and/or fetal hydrops often result in miscarriage, these findings are also compatible with delivery of a viable newborn.55”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Levy, 2021, Outcome of 45,X fetuses with cystic hygroma: a systematic review, Am J Med Genet A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For TS, NIPT sensitivity is 98.8% and specificity is 99.4%, whereas positive predictive value varies widely (range: 9%-85.2%; mean: 25.4%).

    “A recent meta-analysis showed that for TS sensitivity is 98.8% and specificity is 99.4%,61 whereas positive predicted value (PPV) varies widely (range: 9%-85.2%; mean: 25.4%).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [61] Shear, 2023, A systematic review and meta-analysis of cell-free DNA testing for detection of fetal sex chromosome aneuploidy, Prenat Diagn source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When TS is suspected by circulating free DNA, the possible interpretations may include confined placental mosaicism, TS in the fetus, or TS in the mother and co-twin demise of a fetus with TS.

    “When TS is suspected by circulating free DNA, the possible interpretations may include confined placental mosaicism, TS in the fetus, or TS in the mother69-71 and co-twin demise of a fetus with TS.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [69] Bianchi, 2015, Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology, Obstet Gynecol source

      Not checked in the free run.

    • cites [70] Bianchi, 2018, Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results, Genet Med source

      Not checked in the free run.

    • cites [71] Wang, 2015, Maternal mosaicism of sex chromosome causes discordant sex chromosomal aneuploidies associated with noninvasive prenatal testing, Taiwan J Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Legislation on termination of pregnancy varies considerably between countries and lack of consensus regarding choice of termination for TS among fetal medicine experts within countries have been reported.

    “Legislation on termination of pregnancy varies considerably between countries and lack of consensus regarding choice of termination for TS among fetal medicine experts within countries have been reported,80 highlighting the existence of ethical and cultural differences.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [80] Hermann, 2019, Lack of consensus in the choice of termination of pregnancy for Turner syndrome in France, BMC Health Serv Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Average birth weight is ~300-1000 grams below mean and length 1-2 cm below mean for healthy infants of similar gestational age and country of birth.

    “resulting in average birth weight ∼300-1000 grams and length 1-2 cm below mean values for healthy infants of similar gestational age and country of birth.59,138,139”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [59] Viuff, 2015, Only a minority of sex chromosome abnormalities are detected by the Danish national prenatal screening program for Down syndrome, Hum Reprod source

      Not checked in the free run.

    • cites [138] Bernasconi, 1994, Turner's syndrome in Italy: familial characteristics, neonatal data, standards for birth weight and for height and weight from infancy to adulthood, Acta Paediatr source

      Not checked in the free run.

    • cites [139] Isojima, 2009, New reference growth charts for Japanese girls with Turner syndrome, Pediatr Int source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The decline in growth rate is particularly rapid during the first 2 years of life, with an established height deficit by 3 years of age.

    “The decline in growth rate, resulting in downward trend across percentiles, is particularly rapid during the first 2 years of life, with an established height deficit by 3 years of age.140,141”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [140] Even, 2000, Longitudinal analysis of growth over the first 3 years of life in Turner's syndrome, J Pediatr source

      Not checked in the free run.

    • cites [141] Davenport, 2002, Growth failure in early life: an important manifestation of Turner syndrome, Horm Res

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Growth failure in TS begins early, often in utero, characterized by mild intrauterine growth restriction and lower placental weight.

    “Growth failure in TS begins early, often in utero, characterized by mild intrauterine growth restriction,137 and with lower placental weight,59”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [137] FitzSimmons, 1994, Growth parameters in mid-trimester fetal Turner syndrome, Early Hum Dev source

      Not checked in the free run.

    • cites [59] Viuff, 2015, Only a minority of sex chromosome abnormalities are detected by the Danish national prenatal screening program for Down syndrome, Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Overall hypomethylation and gene downregulation is seen in TS across tissues.

    “In general, an overall hypomethylation and gene downregulation is seen in TS across tissues,103”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [103] Viuff, 2023, X chromosome dosage and the genetic impact across human tissues, Genome Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Average adult height in TS ranges from 138 to 147 cm depending on the country, a deficit of ~20 cm (-3 SD) compared with population means.

    “resulting in an average adult height ranging from 138 to 147 cm, depending on the country; this represents a deficit of ∼20 cm (−3 SD) compared with population means for many countries.139,142,143”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [139] Isojima, 2009, New reference growth charts for Japanese girls with Turner syndrome, Pediatr Int source

      Not checked in the free run.

    • cites [142] Lyon, 1985, Growth curve for girls with Turner syndrome, Arch Dis Child source

      Not checked in the free run.

    • cites [143] Rongen-Westerlaken, 1997, Reference values for height, height velocity and weight in Turner's syndrome. Swedish study group for GH treatment, Acta Paediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Short stature in TS affects the limbs more significantly than the trunk, resulting in disproportionate growth with a longer trunk than legs.

    “Short stature in TS affects the limbs more significantly than the trunk, resulting in disproportionate growth, with a longer trunk than legs (increased sitting height to height ratio).152,153”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [152] Rongen Westerlaken, 1993, Body proportions in individuals with Turner syndrome. The Dutch growth hormone working group, Eur J Pediatr source

      Not checked in the free run.

    • cites [153] Uematsu, 1999, Relatively longer hand in patients with Ullrich-Turner syndrome, Am J Med Genet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GH increases height velocity and results in modest increases in adult height for most patients.

    “GH, the primary therapeutic agent, increases height velocity and results in modest increases in adult height for most patients.156”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [156] Baxter, 2007, Recombinant growth hormone for children and adolescents with Turner syndrome, Cochrane Database Syst Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Poor adherence and early treatment discontinuation may result in lower height gain.

    “Poor adherence189 to prescribed doses and early treatment discontinuation190 may also result in lower height gain.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [189] Coutant, 2021, Yearly height gain is dependent on the truly received dose of growth hormone and the duration of periods of poor adherence: practical lessons from the French Easypod™ connect multicenter observational study, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [190] Hughes, 2016, Early cessation and non-response are important and possibly related problems in growth hormone therapy: an OZGROW analysis, Growth Horm IGF Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS appear to be at increased risk of intracranial hypertension, slipped capital femoral epiphysis, and scoliosis during GH treatment compared with children with idiopathic GH deficiency or idiopathic short stature.

    “Individuals with TS appear to be at increased risk of intracranial hypertension and slipped capital femoral epiphysis208 as well as scoliosis173,198,208 during GH treatment compared with children with idiopathic GH deficiency or idiopathic short stature.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [208] Bell, 2010, Long-term safety of recombinant human growth hormone in children, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [173] Maghnie, 2022, Safety and efficacy of pediatric growth hormone therapy: results from the full KIGS cohort, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [198] Coutant, 2021, Effectiveness and overall safety of NutropinAq(®) for growth hormone deficiency and other paediatric growth hormone disorders: completion of the international cooperative growth study, NutropinAq(®) European Registry (iNCGS), Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Early GH treatment in TS prevents further growth failure and provides the opportunity to maintain height within the age-appropriate normal range.

    “Early GH treatment in TS prevents further growth failure162,163,180 and provides the opportunity to maintain height within the age-appropriate normal range.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [162] Davenport, 2007, Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multi-center trial, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [163] Quigley, 2021, Prevention of growth failure in Turner syndrome: long-term results of early growth hormone treatment in the “toddler Turner” cohort, Horm Res Paediatr source

      Not checked in the free run.

    • cites [180] Wasniewska, 2004, Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect, Eur J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Factors predictive of taller adult height include taller baseline height, tall parental heights, younger age at initiation, longer duration of treatment, and higher GH dose.

    “Overall, factors predictive of taller adult height include taller baseline height prior to GH initiation, tall parental heights (ie, mid-parental height), younger age at initiation of therapy, longer duration of treatment (especially pre-pubertal treatment duration) and higher GH dose.162,171,175,176”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [162] Davenport, 2007, Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multi-center trial, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [171] Van Pareren, 2003, Final height in girls with Turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [175] Reiter, 2001, Early initiation of growth hormone treatment allows age-appropriate estrogen use in Turner's syndrome, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [176] Ranke, 2007, Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS, Pediatr Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with TS are inherently at increased risk of disorders of carbohydrate metabolism and have a specific defect in glucose-stimulated insulin secretion.

    “Patients with TS are inherently at increased risk of disorders of carbohydrate metabolism226,227 and have a specific defect in glucose-stimulated insulin secretion.227,228”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [226] Radetti, 2004, Insulin sensitivity in Turner's syndrome: influence of GH treatment, Eur J Endocrinol source

      Not checked in the free run.

    • cites [227] Bakalov, 2004, Impaired insulin secretion in the Turner metabolic syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [228] Caprio, 1991, Insulin resistance: an early metabolic defect of Turner's syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The chance for spontaneous pregnancy in Turner syndrome is about 10%, and it is more common in women with mosaic karyotype.

    “the chance for spontaneous pregnancy is about 10%, again more common in women with mosaic karyotype.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [264] Boechat, 1996, Normal US appearance of ovaries and uterus in four patients with Turner's syndrome and 45,X karyotype, Pediatr Radiol source

      Not checked in the free run.

    • cites [265] Pasquino, 1997, Spontaneous pubertal development in Turner's syndrome. Italian study group for Turner's syndrome, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [266] Hagen, 2010, FSH, LH, inhibin B and estradiol levels in Turner syndrome depend on age and karyotype: longitudinal study of 70 Turner girls with or without spontaneous puberty, Hum Reprod source

      Not checked in the free run.

    • cites [267] Hankus, 2018, Prediction of spontaneous puberty in Turner syndrome based on mid-childhood gonadotropin concentrations, karyotype, and ovary visualization: a longitudinal study, Horm Res Paediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    One double-blind placebo-controlled trial demonstrated a modest synergistic increase in adult height, normalization of the timing of thelarche for about one-quarter of girls, and modest improvements in cognition and memory.

    “One double-blind, placebo-controlled trial using ultra-low-dose oral ethinyl estradiol as a growth-promoting agent during the prepubertal period combined with GH, followed by a standardized incremental pubertal induction regimen, demonstrated a modest synergistic increase in adult height, normalization of the timing of thelarche for about one-quarter of the girls, and modest improvements in cogni”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [160] Ross, 2011, Growth hormone plus childhood low-dose estrogen in Turner's syndrome, N Engl J Med source

      Not checked in the free run.

    • cites [181] Quigley, 2014, Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [254] Ross, 2000, Use of estrogen in young girls with Turner syndrome: effects on memory, Neurology source

      Not checked in the free run.

    • cites [255] Ross, 1998, Effects of estrogen on nonverbal processing speed and motor function in girls with Turner's syndrome, J Clin Endocrinol Metab

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    More than one third of girls with Turner syndrome develop signs of puberty; in non-45,X patients this is twice as common.

    “More than one third of girls with TS develop signs of puberty, in non-45,X patients this is twice as common.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [11] Bryman, 2011, Pregnancy rate and outcome in Swedish women with Turner syndrome, Fertil Steril source

      Not checked in the free run.

    • cites [263] Borgstrom, 2009, Fertility preservation in girls with Turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [264] Boechat, 1996, Normal US appearance of ovaries and uterus in four patients with Turner's syndrome and 45,X karyotype, Pediatr Radiol source

      Not checked in the free run.

    • cites [265] Pasquino, 1997, Spontaneous pubertal development in Turner's syndrome. Italian study group for Turner's syndrome, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [266] Hagen, 2010, FSH, LH, inhibin B and estradiol levels in Turner syndrome depend on age and karyotype: longitudinal study of 70 Turner girls with or without spontaneous puberty, Hum Reprod source

      Not checked in the free run.

    • cites [267] Hankus, 2018, Prediction of spontaneous puberty in Turner syndrome based on mid-childhood gonadotropin concentrations, karyotype, and ovary visualization: a longitudinal study, Horm Res Paediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The methodology to assess impact of GH treatment on QoL in TS is not robust and the data are inconsistent or inconclusive.

    “The methodology to assess impact of GH treatment on QoL in TS is not robust and the data are inconsistent or inconclusive.260-262”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [260] Carel, 2005, Quality of life determinants in young women with Turner's syndrome after growth hormone treatment: results of the StaTur population-based cohort study, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [261] Krantz, 2019, Health-related quality of life in Turner syndrome and the influence of growth hormone therapy: a 20-year follow-up, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [262] Reis, 2018, Systematic review of quality of life in Turner syndrome, Qual Life Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A single 2-year retrospective study showed pegylated GH was comparable to daily GH injections in growth promotion, without unexpected serious adverse effects.

    “A single 2-year retrospective study showed that pegylated GH was comparable to daily GH injections in terms of growth promotion, without unexpected serious adverse effects.257”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [257] Gao, 2022, First clinical study on long-acting growth hormone therapy in children with Turner sydrome, Horm Metab Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both ultrasound ovarian visualization and uterine volume in comparison to prepubertal controls did not help predict spontaneous puberty.

    “Both ultrasound ovarian visualization267 and uterine volume in comparison to prepubertal controls277 did not help predict spontaneous puberty.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [267] Hankus, 2018, Prediction of spontaneous puberty in Turner syndrome based on mid-childhood gonadotropin concentrations, karyotype, and ovary visualization: a longitudinal study, Horm Res Paediatr source

      Not checked in the free run.

    • cites [277] Obara-Moszynska, 2021, Uterine development during induced puberty in girls with Turner syndrome, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There have been few studies comparing the efficacy of oral and transdermal E2 and minimal evidence to guide choice of formulation.

    “There have been few studies comparing the efficacy of oral and transdermal (TD) E2 and minimal evidence to guide choice of formulation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [284] Cameron-Pimblett, 2019, Effects of estrogen therapies on outcomes in Turner syndrome: assessment of induction of puberty and adult estrogen use, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estradiol valerate may be used because it is quickly converted to E2 in the gut and liver and provides stable serum E2 concentrations.

    “Estradiol valerate may also be used because it is quickly converted to E2 in the gut and liver and provides stable serum E2 concentrations.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [282] Giordano Imbroll, 2020, A current perspective into young female sex hormone replacement: a review, Expert Rev Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    17β-estradiol tends to lower blood pressure, improve liver function tests, and increase HDL cholesterol in women with Turner syndrome.

    “In addition, it tends to lower BP, improve liver function tests, and increase HDL cholesterol in women with TS.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [279] Backeljauw, 2019, Sex hormone replacement therapy for individuals with Turner syndrome, Am J Med Genet C Semin Med Genet source

      Not checked in the free run.

    • cites [280] Cintron, 2017, Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis, Endocrine source

      Not checked in the free run.

    • cites [281] Dowlut-McElroy, 2022, The care of adolescents and young adults with Turner syndrome: a pediatric and adolescent gynecology perspective, J Pediatr Adolesc Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    17β-estradiol has been shown to be effective in maintaining and improving bone mineral density, increasing uterine size, and has some beneficial effects on endpoints relating to cardiovascular outcomes.

    “It has been shown to be effective in maintaining and improving BMD, increasing uterine size and has some beneficial effects on endpoints relating to cardiovascular outcomes.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [279] Backeljauw, 2019, Sex hormone replacement therapy for individuals with Turner syndrome, Am J Med Genet C Semin Med Genet source

      Not checked in the free run.

    • cites [280] Cintron, 2017, Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis, Endocrine source

      Not checked in the free run.

    • cites [281] Dowlut-McElroy, 2022, The care of adolescents and young adults with Turner syndrome: a pediatric and adolescent gynecology perspective, J Pediatr Adolesc Gynecol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Several schemes for dosing have been published over the last few years to mimic the diurnal variation and require multiple dose changes and patch applications.

    “Several schemes for dosing have been published over the last few years to mimic this diurnal variation and require multiple dose changes and patch applications.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [291] Donaldson, 2019, Optimal pubertal induction in girls with Turner syndrome using either oral or transdermal estradiol: a proposed modern strategy, Horm Res Paediatr source

      Not checked in the free run.

    • cites [292] Verdonk, 2019, Estradiol reference intervals in women during the menstrual cycle, postmenopausal women and men using an LC-MS/MS method, Clin Chim Acta source

      Not checked in the free run.

    • cites [293] Gawlik, 2018, Late-onset puberty induction by transdermal estrogen in Turner syndrome girls-a longitudinal study, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oral E2 gave rise to a greater increase in HDL cholesterol than transdermal E2, indicating a potential cardioprotective effect.

    “However, oral E2 gave rise to a greater increase in HDL cholesterol than TD E2 indicating a potential cardioprotective effect”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [280] Cintron, 2017, Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis, Endocrine source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Genotoxic estrogens are mutagenic metabolites which have been linked to breast carcinogenesis in post-menopausal women.

    “Genotoxic estrogens are mutagenic metabolites which have been linked to breast carcinogenesis in post-menopausal women.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [285] Mauras, 2019, Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A large recent review showed the effect of E2 was superior to ethinyl estradiol and conjugated equine estrogens for bone mineral density without difference according to route of administration.

    “A large recent review showed the effect of E2 was superior to ethinyl estradiol and conjugated equine estrogens for BMD without difference according to route of administration.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [280] Cintron, 2017, Effect of estrogen replacement therapy on bone and cardiovascular outcomes in women with Turner syndrome: a systematic review and meta-analysis, Endocrine source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The oral route has long been used and reports on satisfying development of secondary sex characteristics and growth are available.

    “The oral route has long been used and reports on satisfying development of secondary sex characteristics and growth are available.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [289] Labarta, 2012, Individualised vs fixed dose of oral 17beta-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial, Eur J Endocrinol source

      Not checked in the free run.

    • cites [290] Matthews, 2017, Hormone supplementation for pubertal induction in girls, Arch Dis Child source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    The correlation between karyotype and phenotype in Turner syndrome is highly variable, as evidenced by cases of repeated pregnancies in multiple patients with 45,X.

    “Despite this evidence, it is also true that the correlation between karyotype and phenotype is highly variable as evidenced by cases of repeated pregnancies in multiple patients with 45,X.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In healthy older adolescents taking the combined oral contraceptive pill for contraception, a dose of >20 mcg ethinyl estradiol is advised to allow ongoing bone mass accrual.

    “In healthy older adolescents taking the combined oral contraceptive pill for contraception, a dose of >20 mcg ethinyl estradiol is advised to allow ongoing bone mass accrual.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [296] Golden, 2020, Bones and birth control in adolescent girls, J Pediatr Adolesc Gynecol source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    If gonadotropins (FSH in particular) in repeated samples (two or more) measured yearly from age 8-9 years are clearly elevated without any pubertal signs on physical exam, the girl with Turner syndrome will need hormone replacement therapy.

    “If gonadotropins (FSH in particular) in repeated samples (two or more) measured yearly from age 8-9 years are clearly elevated without any pubertal signs on physical exam, the girl with TS will need HRT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Ethinyl estradiol has an adverse cardiovascular and metabolic profile and, pertinent for women with Turner syndrome, it tends to increase blood pressure and is linked with an increased risk of venous thromboembolism.

    “It also has an adverse cardiovascular and metabolic profile and, pertinent for women with TS, it tends to increase blood pressure and is linked with an increased risk of venous thromboembolism.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [283] Webber, 2017, HRT for women with premature ovarian insufficiency: a comprehensive review, Hum Reprod Open source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patch doses have primarily been adapted to postmenopausal women, making off-label use necessary even though cutting matrix patches into smaller pieces has been shown to work nicely.

    “Patch doses have primarily been adapted to postmenopausal women, making off-label use necessary even though cutting matrix patches into smaller pieces has been shown to work nicely.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [287] Ankarberg-Lindgren, 2001, Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [288] Ankarberg-Lindgren, 2019, Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures, Endocr Connect source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    E2 values in typical menstruating women depend on phase of cycle with great variability between women and between cycles; follicular and luteal mean E2 values are around 183 and 521 pmol L−1 (50 and 142 pg mL−1), respectively.

    “E2 values in typical menstruating women depend on phase of cycle with great variability between women and between cycles; with follicular and luteal mean E2 values around 183 and 521 pmol L−1 (50 and 142 pg mL−1), respectively.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [286] Taboada, 2011, Pharmacokinetics and pharmacodynamics of oral and transdermal 17beta estradiol in girls with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the UK, access and availability to all treatment options was recognized as an important factor for shared decision-making which can improve medication adherence.

    “In the UK, it was recognized that access and availability to all treatment options was an important factor for shared decision-making which can improve medication adherence.313”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [313] Briggs, 2022, Consensus-led recommendations supporting choice and personalisation of hormone replacement therapy in menopause care, Post Reprod Health source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Progesterone has other effects being crucially important for the implantation of the fertilized ovum, the maintenance of pregnancy, and some psychopharmacological actions including anxiolytic, antidepressant, and analgesic effects.

    “Progesterone has other effects being crucially important for the implantation of the fertilized ovum, the maintenance of pregnancy,298 and some psychopharmacological actions including anxiolytic, antidepressant, and analgesic effects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [298] Stanczyk, 2013, Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects, Endocr Rev source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Higher estrogen doses are particularly important for achieving maximal uterine growth and development as options for fertility treatment increase.

    “This is particularly important for achieving maximal uterine growth and development as options for fertility treatment increase.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [300] Panay, 2020, Premature ovarian insufficiency: an international menopause society white paper, Climacteric source

      Not checked in the free run.

    • cites [301] Cleemann, 2017, Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial, Eur J Endocrinol source

      Not checked in the free run.

    • cites [302] Burt, 2019, Reduced uterine volume after induction of puberty in women with hypogonadism, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [303] Viuff, 2022, Women with Turner syndrome are both estrogen and androgen deficient—the impact of hormone replacement therapy, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Viuff et al. reported that E2 concentrations during hormone replacement therapy in Turner syndrome were comparable to controls only at early follicular phase, suggesting that the current regimen does not fully normalize E2 concentrations in Turner syndrome.

    “Viuff et al. reported that E2 concentrations during HRT in TS were comparable to controls only at early follicular phase suggesting that the current regimen does not fully normalize E2 concentrations in TS.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [303] Viuff, 2022, Women with Turner syndrome are both estrogen and androgen deficient—the impact of hormone replacement therapy, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    More detailed data from healthy adult women confirmed E2 values of 100-181-730 pmol L−1 (27-49-199 pg mL−1) for early-mid-late-follicular phase and 386-599-395 pmol L−1 (105-163-108 pg mL−1) for early-mid-late-luteal phase, with wide variability and some women showing values as high as 2500 pmol L−1.

    “More detailed data coming from healthy adult women confirmed it as well: 100-181-730 pmol L−1 (27-49-199 pg mL−1) for early-mid-late-follicular phase and 386-599-395 pmol L−1 (105-163-108 pg mL−1) for early-mid-late- luteal phase, respectively314 but with wide variability with some women showing values as high as 2500 pmol L−1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [314] Dam, 2022, Muscle performance during the menstrual cycle correlates with psychological well-being, but not fluctuations in sex hormones, Med Sci Sports Exerc source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A suggested adult target is an E2 concentration of 350-500 pmol L−1 (100-150 pg mL−1).

    “A suggested adult target is an E2 concentration of 350-500 pmol L−1 (100-150 pg mL−1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [286] Taboada, 2011, Pharmacokinetics and pharmacodynamics of oral and transdermal 17beta estradiol in girls with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The percentage of annual BMI increment was positive for all progestins used in Turner syndrome women, but levonorgestrel seemed to best prevent weight gain over time.

    “The percentage of annual BMI increment was positive for all progestins used in TS women, but levonorgestrel seemed to best prevent weight gain over time.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [311] Mathez, 2020, Levonorgestrel correlates with less weight gain than other progestins during hormonal replacement therapy in Turner syndrome patients, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dosing schedules are clear for micronized progesterone and medroxyprogesterone acetate but there is a lack of evidence for other progestins.

    “Dosing schedules are clear for micronized progesterone and medroxyprogesterone acetate300 but there is a lack of evidence for other progestins.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [300] Panay, 2020, Premature ovarian insufficiency: an international menopause society white paper, Climacteric source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a study of 145 women with premature ovarian insufficiency, long-term transdermal E2 100 mcg daily restored mean bone mineral density to normal ranges and there was no benefit of increasing the dose to 150 mcg.

    “In contrast, in a study of 145 women with premature ovarian insufficiency, long-term TD E2 100 mcg daily restored mean BMD to normal ranges and there was no benefit of increasing the dose to 150 mcg.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [317] Costa, 2023, Impact of hormone therapy on the bone density of women with premature ovarian insufficiency: a systematic review, Maturitas source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A study with transdermal E2 compared with oral E2 showed that a higher dose corresponded to higher concentration of E2, however without linear correlation.

    “A study with TD E2 compared with oral E2 showed that a higher dose corresponded to higher concentration of E2, however without linear correlation.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [286] Taboada, 2011, Pharmacokinetics and pharmacodynamics of oral and transdermal 17beta estradiol in girls with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In postmenopausal women, micronized progesterone at these doses seems to be devoid of adverse effects on blood pressure, lipid profile, breast cancer risk, and thrombotic risk.

    “In postmenopausal women, this dose seems to be devoid of adverse effects on BP, lipid profile, breast cancer risk, and thrombotic risk.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [300] Panay, 2020, Premature ovarian insufficiency: an international menopause society white paper, Climacteric source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Natural progesterone has poor oral bioavailability but this can be greatly improved by micronizing.

    “Natural progesterone has poor oral bioavailability but this can be greatly improved by micronizing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [298] Stanczyk, 2013, Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects, Endocr Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This study was a cross-sectional, non-controlled retrospective cohort study of 111 patients with Turner syndrome who started estrogen at 15.8 years old.

    “This was a cross-sectional, non-controlled retrospective cohort study of 111 patients with TS who started estrogen at 15.8 years old.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [311] Mathez, 2020, Levonorgestrel correlates with less weight gain than other progestins during hormonal replacement therapy in Turner syndrome patients, Sci Rep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Progesterone can be administered vaginally and exerts good endometrial protective effects at low serum concentrations, although there is limited evidence assessing the efficacy and optimal regimen.

    “Progesterone can be administered vaginally and exerts good endometrial protective effects at low serum concentrations, although there is limited evidence assessing the efficacy and optimal regimen.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [300] Panay, 2020, Premature ovarian insufficiency: an international menopause society white paper, Climacteric source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Progesterone itself has its major effects on the progesterone receptor with negligible effects on the glucocorticoid receptor, androgen receptor, and it is an antagonist of the mineralocorticoid receptor.

    “Progesterone itself has its major effects on the progesterone receptor (PR) with negligible effects on the glucocorticoid receptor (GR), androgen receptor (AR), and it is an antagonist of the mineralocorticoid receptor (MR).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [298] Stanczyk, 2013, Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects, Endocr Rev source

      Not checked in the free run.

    • cites [299] Hipolito Rodrigues, 2021, Micronized progesterone, progestins, and menopause hormone therapy, Women Health source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Medroxyprogesterone acetate has been widely used in hormone replacement therapy because its oral bioavailability is >90%, it has high potency, and its half-life is 24 hours, allowing for daily dosing.

    “Medroxyprogesterone acetate has been widely used in HRT because its bioavailability orally is >90%, it has high potency and its half-life is 24 h, allowing for daily dosing.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [298] Stanczyk, 2013, Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects, Endocr Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Arab region, the most commonly available forms of estrogen were conjugated estrogen (29% of centers) followed by ethinyl estradiol (26%), and the combined oral contraceptive pill was available in 32% of centers.

    “Availability in the Arab region has recently been published312 and showed that the most commonly available forms of estrogen were conjugated estrogen (29% of centers) followed by ethinyl estradiol (26%). The combined oral contraceptive pill was available in 32% centers.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [312] Deeb, 2022, Availability and access to medications for puberty induction and maintenance in adolescents with hypogonadism in the Arab Region, Int J Clin Pract source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    All synthetic progestins bind to the progesterone receptor effectively but differ in their binding affinities and effects on the glucocorticoid, androgen, and mineralocorticoid receptors, giving rise to different profiles of actions and side effects.

    “All synthetic progestins bind to the PR effectively but differ in their binding affinities and effects on the GR, AR, and MR giving rise to different profiles of actions and side effects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [298] Stanczyk, 2013, Progestogens used in postmenopausal hormone therapy: differences in their pharmacological properties, intracellular actions, and clinical effects, Endocr Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both duration of HRT and E2 dose are important for uterine volume and BMD increase.

    “Both duration of HRT as well as E2 dose are important for uterine volume and BMD increase.301,321”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [301] Cleemann, 2017, Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial, Eur J Endocrinol source

      Not checked in the free run.

    • cites [321] Cleemann, 2020, Effect of dosage of 17beta-estradiol on uterine growth in Turner syndrome—a randomized controlled clinical pilot trial, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HRT is important for continuing bone mass accrual to reach peak bone mass during the third decade and for further uterine growth and development.

    “During adulthood the aim is to restore the physiological hormonal environment as closely as possible and HRT is important for continuing bone mass accrual to reach peak bone mass during the third decade and for further uterine growth and development.326,327”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [326] Klein, 2018, Estrogen replacement in Turner syndrome: literature review and practical considerations, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [327] Son, 2019, The efficacy of long-term estrogen replacement therapy in Turner syndrome women with premature ovarian insufficiency, J Pediatr Adolesc Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Maintenance HRT after pubertal induction is continued until the expected age of natural menopause, about 50-55 years, but lower in some populations, aiming for at least 42 years of exogenous estrogen exposure.

    “After completing pubertal induction, maintenance HRT is continued until the expected age of natural menopause, about 50-55 years, but lower in some populations,324,325 aiming for a period of at least 42 years of exogenous estrogen exposure mimicking normal physiology of endogenous estrogen exposure.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [324] Jivraj, 2021, Turner syndrome through the lens of a gynaecologist, Post Reprod Health source

      Not checked in the free run.

    • cites [325] Schoenaker, 2014, Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents, Int J Epidemiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Uterine size during induction of puberty can be a proxy for sufficient estrogen exposure and therefore valuable in addition to serum E2, or when serum E2 cannot be assessed.

    “Uterine size during induction of puberty can be a proxy for sufficient estrogen exposure and therefore valuable in addition to serum E2, or when serum E2 cannot be assessed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [323] Lindsay Mart, 2023, Current recommended estrogen dosing for pubertal induction in Turner syndrome results in normal uterine growth, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The most important challenge is to individualize treatment so that the hypogonadal woman can accept and adhere to her lifelong HRT.

    “Even though endocrinologists discuss E2 form, administration route and dose, the most important challenge is probably to individualize treatment in such a way that the hypogonadal woman can accept and adhere to her lifelong HRT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Uterine volume and endometrial assessments by ultrasound are operator dependent and more difficult to standardize, while MRI is superior in determining uterine volume, yet more expensive.

    “It is important to note that uterine volume and endometrial assessments by ultrasound are operator dependent and more difficult to standardize, while MRI is superior in determining uterine volume, yet more expensive.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [322] Cleemann, 2011, Uterus and ovaries in girls and young women with Turner syndrome evaluated by ultrasound and magnetic resonance imaging, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    E2 dosage affects uterine volume initially but not in the long term.

    “E2 dosage affects uterine volume initially but not in the long term.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [321] Cleemann, 2020, Effect of dosage of 17beta-estradiol on uterine growth in Turner syndrome—a randomized controlled clinical pilot trial, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Estimated daily dose equivalence from the literature are 50/100 μg TD = 2 mg oral E2 = 20 μg ethinyl estradiol.

    “Estimated daily dose equivalence from the literature (depending on assays and clinical endpoints) are 50/100 µg TD = 2 mg oral E2 = 20 µg ethinyl estradiol.290”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [290] Matthews, 2017, Hormone supplementation for pubertal induction in girls, Arch Dis Child source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is a very low risk of breast cancer in TS patients with no significant increase in those treated with standard doses of HRT.

    “There is a very low risk of breast cancer in TS patients with no significant increase in those treated with standard doses of HRT.332,333”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [332] Viuff, 2021, Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy, Eur J Endocrinol source

      Not checked in the free run.

    • cites [333] Bosze, 2006, Hormone replacement and the risk of breast cancer in Turner's syndrome, N Engl J Med source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxandrolone use in TS to promote growth is well-described.

    “Oxandrolone use in TS to promote growth is well-described.249,250”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [249] Gault, 2011, Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial, BMJ source

      Not checked in the free run.

    • cites [250] Mohamed, 2019, Oxandrolone for growth hormone-treated girls aged up to 18 years with Turner syndrome, Cochrane Database Syst Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxandrolone use is not considered standard of care and was reserved for very short girls.

    “However, its use is not considered standard of care and was reserved for very short girls.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [249] Gault, 2011, Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial, BMJ source

      Not checked in the free run.

    • cites [250] Mohamed, 2019, Oxandrolone for growth hormone-treated girls aged up to 18 years with Turner syndrome, Cochrane Database Syst Rev

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ART improved BMD, increased lean body mass, and decreased fat mass.

    “Moreover, it improved BMD, increased lean body mass, and decreased fat mass.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [381] Zuckerman-Levin, 2009, Androgen replacement therapy in Turner syndrome: a pilot study, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    For pubertal induction in girls with TS, mimicking physiology as closely as possible supports linear growth and gradually induces puberty at an age and tempo within the normal range for peers.

    “For pubertal induction in girls with TS it is important to mimic physiology as closely as possible to support linear growth and gradually induce puberty at an age and tempo within the normal range for peers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Patients reported improved QoL, including general health, coping with stress, and sexual desire.

    “Their patients reported improved QoL, including general health, coping with stress, and sexual desire.381”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [381] Zuckerman-Levin, 2009, Androgen replacement therapy in Turner syndrome: a pilot study, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ART improved attention, reaction time, and verbal memory, but had no effect on executive functions and spatial cognition.

    “ART improved attention, reaction time, and verbal memory, but had no effect on executive functions and spatial cognition.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [381] Zuckerman-Levin, 2009, Androgen replacement therapy in Turner syndrome: a pilot study, J Clin Endocrinol Metab source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CHD occurs in approximately half of individuals with TS, including BAV, aortic coarctation, and an arteriopathy that can lead to rare but often fatal aortic dissections.

    “CHD occurs in approximately half of individuals with TS, including BAV, aortic coarctation, and an arteriopathy that can lead to rare but often fatal aortic dissections.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [3] Bondy, 2007, Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [356] Mortensen, 2012, Cardiovascular phenotype in Turner syndrome—integrating cardiology, genetics, and endocrinology, Endocr Rev source

      Not checked in the free run.

    • cites [385] Mazzanti, 1998, Congenital heart disease in patients with Turner's syndrome. Italian study group for Turner syndrome (ISGTS), J

      Not checked in the free run.

    • cites [386] Sybert, 1998, Cardiovascular malformations and complications in Turner syndrome, Pediatrics source

      Not checked in the free run.

    • cites [387] Volkl, 2005, Cardiovascular anomalies in children and young adults with Ullrich-Turner syndrome the Erlangen experience, Clin Cardiol source

      Not checked in the free run.

    • cites [388] Kim, 2011, Cardiovascular anomalies in Turner syndrome: spectrum, prevalence, and cardiac MRI findings in a pediatric and young adult population, AJR Am J Roentgenol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Mimicking physiology during pubertal induction is important for psychosocial well-being, bone health, uterine growth, pregnancy outcomes, and possible neurocognitive benefits.

    “This is important for psychosocial well-being, bone health, uterine growth, pregnancy outcomes, and possible neurocognitive benefits.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The lifetime prevalence of thoracic aortic aneurysms is approximately 25%.

    “The lifetime prevalence of thoracic aortic aneurysms is approximately 25%.382,383”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [382] Meccanici, 2023, Prevalence and development of aortic dilation and dissection in women with Turner syndrome: a systematic review and meta-analysis, Expert Rev Cardiovasc Ther source

      Not checked in the free run.

    • cites [383] Lopez, 2008, Turner syndrome is an independent risk factor for aortic dilation in the young, Pediatrics source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prevalence of CHD in TS ranges from 40%-60%, most commonly left-sided obstructive lesions such as BAV and coarctation.

    “Depending on the age and the imaging technique used, the prevalence of CHD in TS ranges from 40%-60%, most commonly left-sided obstructive lesions such as BAV and coarctation (Table 11).3,356,385-388”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [3] Bondy, 2007, Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [356] Mortensen, 2012, Cardiovascular phenotype in Turner syndrome—integrating cardiology, genetics, and endocrinology, Endocr Rev source

      Not checked in the free run.

    • cites [385] Mazzanti, 1998, Congenital heart disease in patients with Turner's syndrome. Italian study group for Turner syndrome (ISGTS), J

      Not checked in the free run.

    • cites [386] Sybert, 1998, Cardiovascular malformations and complications in Turner syndrome, Pediatrics source

      Not checked in the free run.

    • cites [387] Volkl, 2005, Cardiovascular anomalies in children and young adults with Ullrich-Turner syndrome the Erlangen experience, Clin Cardiol source

      Not checked in the free run.

    • cites [388] Kim, 2011, Cardiovascular anomalies in Turner syndrome: spectrum, prevalence, and cardiac MRI findings in a pediatric and young adult population, AJR Am J Roentgenol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS frequently cope with a lifelong burden of congenital and acquired cardiovascular diseases, which are primarily responsible for the increased mortality of adults with TS.

    “Individuals with TS frequently cope with a lifelong burden of congenital and acquired cardiovascular diseases, which are primarily responsible for the increased mortality of adults with TS.27,28”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Schoemaker, 2008, Mortality in women with Turner syndrome in Great Britain: a national cohort study, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [28] Stochholm, 2006, Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TTE is valuable for the diagnosis and surveillance of CHD and aortic dilation, but may be limited by poor acoustic windows, especially in older children and adults.

    “TTE is valuable for the diagnosis and surveillance of CHD and aortic dilation,426-428 but may be limited by poor acoustic windows, especially in older children and adults.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [426] Yetman, 2018, Clinical and echocardiographic prevalence and detection of congenital and acquired cardiac abnormalities in girls and women with the Turner syndrome, Am J Cardiol source

      Not checked in the free run.

    • cites [427] Lanzarini, 2007, Aortic dimensions in Turner's syndrome: two-dimensional echocardiography versus magnetic resonance imaging, J Cardiovasc Med (Hagerstown ) source

      Not checked in the free run.

    • cites [428] Miller, 1983, Echocardiography reveals a high incidence of bicuspid aortic valve in Turner syndrome, J Pediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unusual coronary anatomy may necessitate modifications to the operative approach and can lead to adverse surgical outcomes in individuals with undetected coronary anomalies.

    “The cardiovascular surgeon needs to be aware of unusual coronary anatomy because it may necessitate modifications to the operative approach and can lead to adverse surgical outcomes in individuals with undetected coronary anomalies.398”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [398] Naito, 2018, The impact of coronary anomalies on the outcome in aortic valve surgery: comparison of bicuspid aortic valve versus tricuspid aortic valve morphotype, Interact Cardiovasc Thorac Surg source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CMR is superior to TTE for the diagnosis of BAV, aortic dilation and aortic arch anomalies while also providing important data on shunt fractions and ventricular volumes.

    “CMR is also superior to TTE for the diagnosis of BAV, aortic dilation and aortic arch anomalies395,429-433 while also providing important data on shunt fractions and ventricular volumes that may inform clinical management.388”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [395] Ho, 2004, Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features, Circulation source

      Not checked in the free run.

    • cites [429] Krikščiūnienė, 2019, Relationship between echocardiographic and magnetic resonance-derived measurements of the thoracic aorta in Turner syndrome patients, Int J Endocrinol source

      Not checked in the free run.

    • cites [430] Somerville, 2016, Cardiac magnetic resonance imaging in pediatric Turner syndrome, J Pediatr source

      Not checked in the free run.

    • cites [431] Nejatian, 2015, Aortic measurements in patients with aortopathy are larger and more reproducible by cardiac magnetic resonance compared with echocardiography, Pediatr Cardiol source

      Not checked in the free run.

    • cites [432] Ostberg, 2004, A comparison of echocardiography and magnetic resonance imaging in cardiovascular screening of adults with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [433] De Groote, 2014, Abnormal aortic arch morphology in Turner syndrome patients is a risk factor for hypertension, Heart Vessels source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BAV is frequently associated with thoracic aortic dilation, coronary anomalies, coarctation, and other left-sided congenital lesions.

    “BAV is frequently associated with thoracic aortic dilation, coronary anomalies, coarctation, and other left-sided congenital lesions,406 which should be actively screened for if BAV is identified.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [406] Szöcs, 2022, Concomitant cardiovascular malformations in isolated bicuspid aortic valve disease: a retrospective cross-sectional study and meta-analysis, Cardiovasc Diagn Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CMR is not constrained by anatomic factors and is thus more sensitive for extra-cardiac lesions such as partial anomalous pulmonary venous return.

    “CMR is not constrained by anatomic factors and is thus more sensitive for extra-cardiac lesions such as partial anomalous pulmonary venous return.388,395,420”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [388] Kim, 2011, Cardiovascular anomalies in Turner syndrome: spectrum, prevalence, and cardiac MRI findings in a pediatric and young adult population, AJR Am J Roentgenol source

      Not checked in the free run.

    • cites [395] Ho, 2004, Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features, Circulation source

      Not checked in the free run.

    • cites [420] van den Hoven, 2017, Partial anomalous pulmonary venous return in Turner syndrome, Eur J Radiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Imaging remains underutilized and not systematically applied.

    “Non-invasive imaging is an essential part of cardiovascular screening and surveillance across the life span of individuals with TS,233,388,396,418-423 but imaging remains underutilized and not systematically applied.420,424”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [420] van den Hoven, 2017, Partial anomalous pulmonary venous return in Turner syndrome, Eur J Radiol source

      Not checked in the free run.

    • cites [424] Kahlert, 2019, Deficient knowledge in adult care as an incentives for founding Turner centers in Germany, Endocr Connect source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Seventy percent of aortic dissections originate in the ascending aorta (Type A), and 30% of dissections originate in the descending thoracic aorta (Type B).

    “Seventy percent of aortic dissections originate in the ascending aorta (Type A), and 30% of dissections originate in the descending thoracic aorta (Type B).434”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [434] Meccanici, 2022, Aortic dilation and growth in women with Turner syndrome, Heart source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Median postoperative hospital stays, reoperation rates, and mortality are increased compared to non-TS patients.

    “Median postoperative hospital stays, reoperation rates, and mortality are increased compared to non-TS patients.414-416”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [414] Fuchs, 2019, Long-term outcomes in patients with Turner syndrome: a 68-year follow-up, J Am Heart Assoc source

      Not checked in the free run.

    • cites [415] Cramer, 2014, The spectrum of congenital heart disease and outcomes after surgical repair among children with Turner syndrome: a single-center review, Pediatr Cardiol source

      Not checked in the free run.

    • cites [416] Ribé, 2023, Outcomes of cardiothoracic surgery in women with Turner syndrome, Ann Cardiothorac Surg source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The incidence of aortic dissection in TS is approximately 164 per 100 000 person-years, compared to 6 per 100 000 person-years in the general population.

    “The incidence of aortic dissection in TS is approximately 164 per 100 000 person–years, compared to 6 per 100 000 person–years in the general population.382”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [382] Meccanici, 2023, Prevalence and development of aortic dilation and dissection in women with Turner syndrome: a systematic review and meta-analysis, Expert Rev Cardiovasc Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BAV is detected in more than 25% of individuals with TS, or 50 times the rate in the general population.

    “BAV is detected in more than 25% of individuals with TS, or 50 times the rate in the general population.404”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [404] Olivieri, 2013, Spectrum of aortic valve abnormalities associated with aortic dilation across age groups in Turner syndrome, Circ Cardiovasc Imaging source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Percutaneous treatment of aortic coarctation, although effective, may be associated with significant morbidity and mortality due to increased risk for aortic dissection with a percutaneous approach.

    “Percutaneous treatment of aortic coarctation, although effective, may be associated with significant morbidity and mortality due to increased risk for aortic dissection with a percutaneous approach.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [417] van den Hoven, 2017, Adverse outcome of coarctation stenting in patients with Turner syndrome, Catheter Cardiovasc Interv source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypertension is three to four times more prevalent in individuals with TS than in matched controls and does not vary significantly by karyotype.

    “Hypertension is three to four times more prevalent in individuals with TS than in matched controls and does not vary significantly by karyotype.450-452”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [450] Lebenthal, 2018, The natural history of metabolic comorbidities in Turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes, Front Endocrinol (Lausanne) source

      Not checked in the free run.

    • cites [451] Lin, 2019, Recognition and management of adults with Turner syndrome: from the transition of adolescence through the senior years, Am J Med Genet A source

      Not checked in the free run.

    • cites [452] Sandahl, 2020, Natural history of hypertension in Turner syndrome during a 12-year pragmatic interventional study, Hypertension source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Coagulation is generally normal when evaluated in large TS cohorts, and in general TS does not seem to be an independent risk factor for venous thrombosis.

    “Coagulation is generally normal when evaluated in large TS cohorts, and in general TS does not seem to be an independent risk factor for venous thrombosis.29”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Viuff, 2020, Sex hormone replacement therapy in Turner syndrome—impact on morbidity and mortality, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The intrinsic shape of the aorta in individuals with TS who do not have coarctation may contribute to the etiology of hypertension and can become more accentuated over time as the aorta elongates.

    “The intrinsic shape of the aorta in individuals with TS who do not have coarctation may also contribute to the etiology of hypertension and can become more accentuated over time as the aorta elongates.433”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [433] De Groote, 2014, Abnormal aortic arch morphology in Turner syndrome patients is a risk factor for hypertension, Heart Vessels source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prevalence of hypertension is as high as 20%-40% in children and up to 60% in adults with TS.

    “The prevalence of hypertension is as high as 20%-40% in children441,453 and up to 60% in adults with TS.357,452,454-456”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [441] Los, 2016, Pilot study of blood pressure in girls with Turner syndrome: an awareness gap, clinical associations, and new hypotheses, Hypertension source

      Not checked in the free run.

    • cites [453] McCarrison, 2023, The prevalence of hypertension in paediatric Turner syndrome: a systematic review and meta-analysis, J Hum Hypertens source

      Not checked in the free run.

    • cites [357] Gravholt, 1998, Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement, Diabetes Care source

      Not checked in the free run.

    • cites [452] Sandahl, 2020, Natural history of hypertension in Turner syndrome during a 12-year pragmatic interventional study, Hypertension source

      Not checked in the free run.

    • cites [454] Gravholt, 2006, Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome, J Hypertens source

      Not checked in the free run.

    • cites [455] Landin-Wilhelmsen, 2001, Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [456] Elsheikh, 2001, Hypertension is a major risk factor for aortic root dilatation in women with Turner's syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    A rapid rate of aortic dilation (>3 mm year−1) may also be a risk factor for dissection.

    “A rapid rate of aortic dilation (>3 mm year−1) may also be a risk factor for dissection, but this has not been validated in TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    There is some evidence that blood pressure may be substantially lower with TD E2 preparations compared to oral ethinyl E2, but this has not been tested specifically in TS.

    “There is some evidence that blood pressure may be substantially lower with TD E2 preparations compared to oral ethinyl E2, but this has not been tested specifically in TS.359”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [359] Langrish, 2009, Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure, Hypertension source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While increased levels of procoagulant factors and reduced protein C and S were reported in some individuals with TS, most studies have reported normal levels of clotting factors, fibrinolytic factors, and clotting times.

    “While increased levels of procoagulant factors and reduced protein C and S were reported in some individuals with TS,129,474 most studies have reported normal levels of clotting factors, fibrinolytic factors, and clotting times.455”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [129] Calcaterra, 2011, Thrombophilic screening in Turner syndrome, J Endocrinol Invest

      Not checked in the free run.

    • cites [474] Gravholt, 2012, Coagulation and fibrinolytic disturbances are related to carotid intima thickness and arterial blood pressure in Turner syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [455] Landin-Wilhelmsen, 2001, Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Systemic hypertension appears at early ages and progresses in frequency and severity throughout adulthood in TS.

    “Systemic hypertension appears at early ages and progresses in frequency and severity throughout adulthood.384,450”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

    • cites [450] Lebenthal, 2018, The natural history of metabolic comorbidities in Turner syndrome from childhood to early adulthood: comparison between 45,X monosomy and other karyotypes, Front Endocrinol (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    These indexing methods only apply to the ascending aorta, and ASI or Z-scores should only be used to guide medical decisions for adults who fall within 1-2 standard deviations around the mean BSA of 1.7-1.9 m2 for all adult women.

    “It is important to note that these indexing methods only apply to the ascending aorta, and ASI or Z-scores should only be used to guide medical decisions for adults who fall within 1-2 standard deviations around the mean BSA of 1.7-1.9 m2 for all adult women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hypertension is more frequent in individuals with TS who have dysmorphism, coarctation, or renal anomalies but may also be idiopathic.

    “Hypertension is more frequent in individuals with dysmorphism, coarctation, or renal anomalies but may also be idiopathic.457”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [457] Van De Kelft, 2020, Disproportion and dysmorphism in an adult Belgian population with Turner syndrome: risk factors for chronic diseases?, Acta Clin Belg source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While hypertension is correlated with the presence of aortic dilation in TS, no studies have demonstrated that antihypertensive therapies slow or prevent aortic dilation.

    “While hypertension is correlated with the presence of aortic dilation in TS, no studies have demonstrated that antihypertensive therapies slow or prevent aortic dilation.447,456,458”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [447] De Groote, 2015, Arterial hypertension in Turner syndrome: a review of the literature and a practical approach for diagnosis and treatment, J Hypertens source

      Not checked in the free run.

    • cites [456] Elsheikh, 2001, Hypertension is a major risk factor for aortic root dilatation in women with Turner's syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [458] Jones, 2023, Hypertension in Turner syndrome: a review of proposed mechanisms, management and new directions, J Hypertens source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Individuals with TS and comorbidities often exhibit higher total cholesterol, LDL cholesterol, and triglycerides compared to controls, although severe elevations are infrequently reported.

    “Individuals with TS and comorbidities often exhibit higher total cholesterol, LDL cholesterol, and triglycerides compared to controls, although severe elevations are infrequently reported.331,476”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [331] Sandahl, 2023, A prospective study of lipids in adult women with Turner syndrome, J Endocr Soc source

      Not checked in the free run.

    • cites [476] Kozlowska-Wojciechowska, 2006, Are young women with Turner syndrome at greater risk of coronary artery disease?, Eur J Cardiovasc Prev Rehabil source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is no evidence that multiple gestations are a significant risk factor for aortic complications, although multiple pregnancies and multiple embryo transfers does lead to an increased risk of hypertension, which might contribute to dissection risk.

    “There is no evidence that multiple gestations are a significant risk factor for aortic complications, although multiple pregnancies and multiple embryo transfers does lead to an increased risk of hypertension, which might contribute to dissection risk.514”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [514] Masoudian, 2016, Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: a systematic review and metaanalysis, Am J Obstet Gynecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A higher resting heart rate has been well documented in TS cohorts and has been linked to increased resting sympathetic tone and other features of dysautonomia.

    “A higher resting heart rate has been well documented in TS cohorts and has been linked to increased resting sympathetic tone and other features of dysautonomia.487,488”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [487] Bondy, 2006, Prolongation of the cardiac QTc interval in Turner syndrome, Medicine (Baltimore) source

      Not checked in the free run.

    • cites [488] Sozen, 2008, Atrial and ventricular arryhthmogenic potential in Turner syndrome, Pacing Clin Electrophysiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The individuals in that study also had significantly higher waist circumference, impaired glucose tolerance, and higher blood pressures.

    “However, the individuals in that study also had significantly higher waist circumference, impaired glucose tolerance, and higher blood pressures.477”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [477] O’Gorman, 2013, An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome, Clin Endocrinol (Oxf) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypercholesterolemia is prevalent in TS and is influenced by numerous intrinsic factors, including obesity, metabolic syndrome, and type 1 or type 2 diabetes.

    “Hypercholesterolemia is prevalent in TS and is influenced by numerous intrinsic factors, including obesity, metabolic syndrome, and type 1 or type 2 diabetes.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [331] Sandahl, 2023, A prospective study of lipids in adult women with Turner syndrome, J Endocr Soc source

      Not checked in the free run.

    • cites [476] Kozlowska-Wojciechowska, 2006, Are young women with Turner syndrome at greater risk of coronary artery disease?, Eur J Cardiovasc Prev Rehabil source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While there is no published data about the effects of exercise on vascular disease in TS, aerobic exercise was shown to decrease aortic growth rates in a mouse model of Marfan syndrome and may also be protective in humans.

    “While there is no published data about the effects of exercise on vascular disease in TS, aerobic exercise was shown to decrease aortic growth rates in a mouse model of Marfan syndrome and may also be protective in humans.504,505”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [504] Mas-Stachurska, 2017, Cardiovascular benefits of moderate exercise training in Marfan syndrome: insights from an animal model, J Am Heart Assoc source

      Not checked in the free run.

    • cites [505] Selamet Tierney, 2022, Can 10 000 healthy steps a day slow aortic root dilation in pediatric patients with Marfan syndrome?, J Am Heart Assoc source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In recent surveys, a sedentary lifestyle was reported by more than half of children and adults with TS and was associated with arterial hypertension.

    “In recent surveys, a sedentary lifestyle was reported by more than half of children and adults with TS and was associated with arterial hypertension.496-498”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [496] Santi, 2021, Health behaviour of women with Turner syndrome, Acta Paediatr source

      Not checked in the free run.

    • cites [497] Thompson, 2020, A mixed methods study of physical activity and quality of life in adolescents with Turner syndrome, Am J Med Genet A source

      Not checked in the free run.

    • cites [498] Arnold, 2021, Physical activity and diet quality: effects on cardiovascular morbidity in women with Turner syndrome-results from an online patient survey, J Clin Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies that rely on death certificates to determine causes of death found that the standardized mortality ratio for ischemic heart disease is elevated in TS, with most deaths due to coronary artery disease occurring after age 45.

    “Studies that rely on death certificates to determine causes of death found that the standardized mortality ratio for ischemic heart disease is elevated in TS, with most deaths due to coronary artery disease occurring after age 45.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Schoemaker, 2008, Mortality in women with Turner syndrome in Great Britain: a national cohort study, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These ECG findings are minor in many cases and the clinical implications are not clear.

    “However, these findings are minor in many cases and the clinical implications are not clear.487,490,491”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [487] Bondy, 2006, Prolongation of the cardiac QTc interval in Turner syndrome, Medicine (Baltimore) source

      Not checked in the free run.

    • cites [490] Bondy, 2006, Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome, Pediatrics source

      Not checked in the free run.

    • cites [491] Noordman, 2021, Cardiac abnormalities in girls with Turner syndrome: ECG abnormalities, myocardial strain imaging, and karyotype-phenotype associations, Am J Med Genet A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pre-eclampsia in the general pregnant population is associated with several risk factors, including a family history of pre-eclampsia, nulliparity, older age, elevated BMI, pre-existing diabetes mellitus, chronic renal disease, antiphospholipid antibodies, multiple gestations, and pre-existing hypertension.

    “Pre-eclampsia in the general pregnant population is associated with several risk factors, including a family history of pre-eclampsia, nulliparity, older age, elevated BMI, pre-existing diabetes mellitus, chronic renal disease, antiphospholipid antibodies, multiple gestations, and pre-existing hypertension.525”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [525] Steegers, 2010, Pre-eclampsia, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Aspects of care in individuals with TS that pose barriers to transition unique from other chronic conditions include lower visuospatial processing, lower self-esteem, and difficulties with executive functioning.

    “There are aspects of care in individuals with TS that pose barriers to transition that are unique from other chronic conditions, such as lower visuospatial processing and self-esteem, and difficulties with executive functioning.367”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [367] Jordan, 2023, Longitudinal investigation of cognition, social competence, and anxiety in children and adolescents with Turner syndrome, Horm Behav source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Assisted reproductive technologies were proposed to be a risk factor for aortic dilation or dissection, but recent studies did not show any difference in aortic complications.

    “Assisted reproductive technologies were proposed to be a risk factor for aortic dilation or dissection, but recent studies did not show any difference in aortic complications.510”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [510] Grewal, 2021, Cardiovascular outcomes of pregnancy in Turner syndrome, Heart source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Current guidelines recommend counseling against pregnancy only for symptomatic patients with severe aortic stenosis or asymptomatic patients with impaired left ventricular function or an abnormal exercise test; otherwise, pregnancy appears to be well tolerated.

    “Current guidelines recommend counseling against pregnancy only for symptomatic patients with severe aortic stenosis or asymptomatic patients with impaired left ventricular function or an abnormal exercise test.521 Otherwise, pregnancy appears to be well tolerated.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [521] Regitz-Zagrosek, 2018, 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy, Eur Heart J source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hypertension is more common in women with TS throughout the lifespan, which may contribute to the higher incidence of hypertensive complications during pregnancy.

    “Hypertension is more common in women with TS throughout the lifespan, which may contribute to the higher incidence of hypertensive complications during pregnancy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Decreased fetal birth weight may be associated with peripartum use of beta-blockers and fetal growth should be monitored.

    “However, decreased fetal birth weight may be associated with peripartum use of beta-blockers and fetal growth should be monitored.526,527”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [526] Ersbøll, 2014, Treatment with oral beta-blockers during pregnancy complicated by maternal heart disease increases the risk of fetal growth restriction, BJOG source

      Not checked in the free run.

    • cites [527] Ruys, 2014, Cardiac medication during pregnancy, data from the ROPAC, Int J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ROPAC data, cesarean section was not superior to a vaginal delivery in terms of maternal outcomes, but an increase in adverse fetal events was observed.

    “In ROPAC data, cesarean section was not superior to a vaginal delivery in terms of maternal outcomes, but an increase in adverse fetal events was observed.527”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [527] Ruys, 2014, Cardiac medication during pregnancy, data from the ROPAC, Int J Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Measures of transition success have not been well-defined or applied and longitudinal studies have not been conducted.

    “Measures of transition success have not been well-defined or applied531,534,537 and longitudinal studies have not been conducted.537”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [531] Sharma, 2014, Transition care: future directions in education, health policy, and outcomes research, Acad Pediatr source

      Not checked in the free run.

    • cites [534] Prior, 2014, Measuring the “triple aim” in transition care: a systematic review, Pediatrics source

      Not checked in the free run.

    • cites [537] Varty, 2020, A systematic review of transition readiness in youth with chronic disease, West J Nurs Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although there is limited data on TS, a Registry of Pregnancy and Cardiac Disease (ROPAC) study clearly demonstrated that women with moderate to severe aortic stenosis can complete successful pregnancies without fatalities, though some experienced heart failure and required medical interventions.

    “Although there is limited data on TS, a Registry of Pregnancy and Cardiac Disease (ROPAC) study clearly demonstrated that women with moderate to severe aortic stenosis can complete successful pregnancies without fatalities. However, some experienced heart failure and required medical interventions.518”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [518] Orwat, 2016, Risk of pregnancy in moderate and severe aortic stenosis: from the multinational ROPAC registry, J Am Coll Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oocyte donation is not seen as a specific risk factor, but it does confer a 2-3-fold risk of preeclampsia.

    “While oocyte donation is not seen as a specific risk factor, it does confer a 2-3-fold risk of preeclampsia529”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [529] Berntsen, 2021, Pregnancy outcomes following oocyte donation, Best Pract Res Clin Obstet Gynaecol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Data specific to the impact of transition process in the TS population are sparse, though one study showed lower loss to follow up in AYA with TS with organized transition.

    “Data specific to the impact of transition process in the TS population are sparse, though one study showed lower loss to follow up in AYA with TS with organized transition.538”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [538] Bernard, 2019, MANAGEMENT OF ENDOCRINE DISEASE: transition of care for young adult patients with Turner syndrome, Eur J Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The Transition Readiness Assessment Questionnaire 5.0 (TRAQ) is a 20-item validated measure used to examine knowledge and health-related skills.

    “The Transition Readiness Assessment Questionnaire 5.0 (TRAQ) is a 20-item validated measure which is used to examine knowledge and health-related skills (eg, appointment-keeping, managing medications and daily activities, communicating with providers).543”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [543] Sawicki, 2011, Measuring the transition readiness of youth with special healthcare needs: validation of the TRAQ—transition readiness assessment questionnaire, J Pediatr Psychol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Structured transition in AYA with chronic health care needs is shown to be beneficial in a number of specific situations, though data are mixed.

    “Structured transition in AYA with chronic health care needs is shown to be beneficial in a number of specific situations,532,533 though data are mixed.534-536”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [532] White, 2018, Supporting the health care transition from adolescence to adulthood in the medical home, Pediatrics source

      Not checked in the free run.

    • cites [533] Pape, 2022, Health care transition from pediatric to adult care: an evidence-based guideline, Eur J Pediatr source

      Not checked in the free run.

    • cites [534] Prior, 2014, Measuring the “triple aim” in transition care: a systematic review, Pediatrics source

      Not checked in the free run.

    • cites [535] Campbell, 2016, Transition of care for adolescents from paediatric services to adult health services, Cochrane Database Syst Rev

      Not checked in the free run.

    • cites [536] Gabriel, 2017, Outcome evidence for structured pediatric to adult health care transition interventions: a systematic review, J Pediatr source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, which are both observed with strikingly increased frequency in TS.

    “TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, which are both observed with strikingly increased frequency in TS.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Social skill difficulties can impact romantic relationships and sexual experiences.

    “Social skill difficulties can also impact romantic relationships and sexual experiences.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    General guidelines recommend that transition begin between 12 and 14 years of age.

    “General guidelines recommend that transition begin between 12 and 14 years of age, yet developmental age is likely more relevant than chronological age in individuals with TS given the increased neurocognitive and psychosocial differences.424,532,533”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [424] Kahlert, 2019, Deficient knowledge in adult care as an incentives for founding Turner centers in Germany, Endocr Connect source

      Not checked in the free run.

    • cites [532] White, 2018, Supporting the health care transition from adolescence to adulthood in the medical home, Pediatrics source

      Not checked in the free run.

    • cites [533] Pape, 2022, Health care transition from pediatric to adult care: an evidence-based guideline, Eur J Pediatr source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Transition readiness and/or success in individuals with TS seems to differ from other chronic conditions, with distinct requirements including individualization of transition timing and a longer period of caregiver support may be necessary.

    “Transition readiness and/or success in individuals with TS seems to differ from other chronic conditions, with distinct requirements including, but not limited to, individualization of transition timing, and a longer period of caregiver support may be necessary.550”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [550] Streur, 2022, The transition to independence and adult care for women with Turner syndrome: current status and priorities of 1338 women and parents, Am J Med Genet A source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Expectancy bias may influence parents' and adolescents' reports of social skill improvements, as an independent evaluation of their social behavior by teachers did not agree.

    “However, expectancy bias may influence their reports as an independent evaluation of their social behavior by teachers did not agree.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Much of the transition literature highlights the need to identify local adult providers with expertise in TS to optimize care in adulthood.

    “Much of the transition literature highlights the need to identify local adult providers with expertise in TS to optimize care in adulthood.559”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [559] Lucaccioni, 2015, Turner syndrome—issues to consider for transition to adulthood, Br Med Bull source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The period of transition to adulthood is particularly important given the high rates of loss to follow up, complications, and lack of health care access and affordability in adulthood in certain parts of the world.

    “The period of transition to adulthood is particularly important given the high rates of loss to follow up, complications, and lack of health care access and affordability in adulthood in certain parts of the world.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    The transition process is likely optimized with the inclusion of a transition coordinator as a member of the healthcare team.

    “The transition process is likely optimized with the inclusion of a transition coordinator as a member of the healthcare team.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    An accurate summary of the individual's medical history is essential to a successful transfer.

    “An accurate summary of the individual's medical history is essential to a successful transfer, and copies should be provided to the patient, their caregiver (as indicated), the primary care provider, the TS adult healthcare provider, and any relevant subspecialists.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Longitudinal AMH measurements on an annual basis or more frequently provide a more accurate estimate of ovarian reserve than individual values and may show a trend over time.

    “Longitudinal AMH measurements on an annual basis or more frequently if indicated, provide a more accurate estimate of the ovarian reserve than individual values and may show a trend over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Morbidity and mortality in adults with TS are well-described, with a life-long requirement for regular medical care and surveillance.

    “Morbidity and mortality in adults with TS are well-described, with a life-long requirement for regular medical care and surveillance.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [334] Vincent, 2017, Increased detection of co-morbidities with evaluation at a dedicated adult Turner syndrome clinic, Climacteric source

      Not checked in the free run.

    • cites [556] Freriks, 2011, Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    AMH reflects the primordial follicle pool and predicts the reproductive lifespan of women as a key biomarker of ovarian reserve.

    “AMH reflects the primordial follicle pool and predicts the reproductive lifespan of women as a key biomarker of ovarian reserve.580”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [580] Weenen, 2004, Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment, Mol Hum Reprod source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Ovarian stimulation and oocyte cryopreservation is an established method of preserving fertility in adults, and oocyte cryopreservation is no longer considered experimental for AYA undergoing gonadotoxic therapy.

    “Ovarian stimulation and oocyte cryopreservation is an established method of preserving fertility in adults, and oocyte cryopreservation is no longer considered experimental for AYA undergoing gonadotoxic therapy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    This rules out around 85% of patients, because they face primary ovarian insufficiency before that time, leaving OTC as the only option for the majority.

    “This rules out around 85% of patients, because they face primary ovarian insufficiency before that time, leaving OTC as the only option for the majority.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Current options for fertility preservation in girls with TS are oocyte cryopreservation following ovarian stimulation and ovarian tissue cryopreservation following laparoscopy.

    “The current options for fertility preservation in girls with TS are cryopreservation of oocytes retrieved following ovarian stimulation with exogenous gonadotrophin analogues, and ovarian tissue cryopreservation (OTC) retrieved following a laparoscopy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Those with monosomy X could still be fertile enough to undergo ovarian stimulation successfully or become pregnant spontaneously, as a wide variation is seen between karyotype in peripheral cells and ovarian cells.

    “It is important to keep in mind that those with monosomy X could still be fertile enough to undergo ovarian stimulation successfully or become pregnant spontaneously, as a wide variation is seen between karyotype in peripheral cells and ovarian cells.576,609,610”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [576] Nadesapillai, 2021, Why are some patients with 45,X Turner syndrome fertile? A young girl with classical 45,X Turner syndrome and a cryptic mosaicism in the ovary, Fertil Steril source

      Not checked in the free run.

    • cites [609] Peek, 2023, Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model, Fertil Steril source

      Not checked in the free run.

    • cites [610] Peek, 2019, Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells, Hum Reprod source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Individuals with TS without spontaneous puberty may benefit from expert counseling about the range of options for family planning, such as oocyte and embryo donation, use of gestational carrier, adoption, and the choice not to have children.

    “While likely not eligible for oocyte cryopreservation, individuals without spontaneous puberty may benefit from expert counseling about the range of options for family planning, such as oocyte and embryo donation, use of gestational carrier, adoption, and the choice not to have children.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    OTC could be an option for TS patients with favorable predictive factors, such as mosaic karyotype, spontaneous puberty, and detectable AMH and/or FSH <10 IU L−1.

    “Based on these findings, OTC could be an option for TS patients with favorable predictive factors, such as mosaic karyotype, spontaneous puberty, and detectable AMH and/or FSH <10 IU L−1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Ovarian reserve declines as women age, and it could be expected that the younger the girl, the higher the odds of having follicles.

    “Ovarian reserve declines as women ages and it could be expected that the younger the girl, the higher the odds of having follicles.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    It is questionable whether the follicle density after OTT in girls with TS would be sufficient to achieve pregnancy.

    “In this light, it is questionable whether the follicle density after OTT in girls with TS would be sufficient to achieve pregnancy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Information and support needs before and after birth will be different for parents of individuals with TS.

    “Information and support needs before and after birth will be different.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Resources including genetic counseling, consultation with medical specialists in TS, and TS support and advocacy contacts may help caregivers during this potentially vulnerable time.

    “Resources including, but not limited to genetic counseling, consultation with medical specialists in TS, and TS support and advocacy contacts may help caregivers during this potentially vulnerable time.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Behavioral health support through multidisciplinary teams may help patients manage emotional hardship associated with this counseling, undergo healthy mourning in processing infertility and provide support during fertility preservation or treatment if they are pursued.

    “Behavioral health support through multidisciplinary teams may help patients manage emotional hardship associated with this counseling, undergo healthy mourning in processing infertility and provide support during fertility preservation or treatment if they are pursued.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    It is possible that patients with TS will be unable to utilize cryopreserved oocytes and/or ovarian tissue because of health concerns related to pregnancy, or lack resources for storage or fertility treatment.

    “Patients and families should be counseled on the possibility of being unable to utilize cryopreserved oocytes and/or ovarian tissue because of health concerns related to pregnancy, or lack resources for storage or fertility treatment.629”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [629] Blakemore, 2019, Addressing practical concerns surrounding fertility preservation in patients with Turner syndrome, Fertil Steril source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Issues of justice arise because both fertility counseling and preservation consume health care resources.

    “Issues of justice arise because both fertility counseling and preservation consume health care resources.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    High arched and narrow palate, hypotonia, poor coordination, and delay in oral-motor skills can all contribute to feeding and/or swallowing difficulties in infants with TS.

    “High arched and narrow palate, hypotonia, poor coordination, and delay in oral-motor skills can all contribute to feeding and/or swallowing difficulties in infants with TS.637”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [637] Starke, 2003, Parents’ descriptions of development and problems associated with infants with Turner syndrome: a retrospective study, J Paediatr Child Health source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Decisions about fertility preservation for pediatric patients may fall in the zone of parental discretion, in which parents attempt to act in the best interest of the child.

    “Decisions about fertility preservation for pediatric patients may fall in the zone of parental discretion, in which parents attempt to act in the best interest of the child.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Patients who are pre-adolescents or adolescents at the time of decisions about fertility preservation may be too young to discuss future goals for family building, to understand the impact of infertility or to give informed consent for fertility preservation procedures.

    “Patients who are pre-adolescents or adolescents at the time of decisions about fertility preservation may be too young to discuss future goals for family building, to understand the impact of infertility or to give informed consent for fertility preservation procedures.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. The quote only partly states this claim.

    Interpretationreasoning

    Early identification and treatment of glaucoma, cataracts, strabismus, and refractive errors are important to prevent amblyopia and vision loss in TS.

    “Early identification and treatment of glaucoma, cataracts, strabismus, and refractive errors are important to prevent amblyopia and vision loss.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    This counseling may result in grief and hardship.

    “This counseling may result in grief and hardship.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Peripheral lymphedema is thought to contribute to development of nail anomalies such as deeply set, narrow, and hyperconvex nails, affecting 19%-73% of individuals with TS.

    “Meanwhile, peripheral lymphedema is thought to contribute to development of nail anomalies such as deeply set, narrow, and hyperconvex nails, affecting 19%-73% of individuals with TS.673,680,681”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [673] Said, 2022, Dermatologic findings in individuals with Turner syndrome: a cross-sectional study across the lifespan, J Am Acad Dermatol source

      Not checked in the free run.

    • cites [680] Nunes, 2021, Clinical and cytogenetic characteristics of patients diagnosed with Turner syndrome in a clinical genetics service: cross-sectional retrospective study, Sao Paulo Med J source

      Not checked in the free run.

    • cites [681] Zelinska, 2018, Nationwide study of Turner syndrome in Ukrainian children: prevalence, genetic variants and phenotypic features, J Clin Res Pediatr Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Though treatment typically leads to only temporary improvement, it may be useful in preventing further complications such as skin breakdown, ulceration, and infection.

    “Though treatment typically leads to only temporary improvement, it may be useful in preventing further complications such as skin breakdown, ulceration, and infection.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Poor growth, neurodevelopmental delays, and behavioral disorders are associated with untreated obstructive sleep apnea.

    “It is also worth noting that poor growth, neurodevelopmental delays, and behavioral disorders are associated with untreated obstructive sleep apnea.672”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [672] da Silva Gusmão Cardoso, 2018, Cognitive and behavioral effects of obstructive sleep apnea syndrome in children: a systematic literature review, Sleep Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Central lymphedema may contribute to the development of congenital heart anomalies in TS as well as webbed neck (pterygium colli).

    “Central lymphedema may contribute to the development of congenital heart anomalies in TS as well as webbed neck (pterygium colli).393”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [393] Loscalzo, 2005, Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome, Pediatrics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Lymphedema may be managed supportively using techniques that encourage lymphatic drainage including compression garments and lymphatic massage.

    “Lymphedema may be managed supportively using techniques that encourage lymphatic drainage including compression garments and lymphatic massage.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    This combination has a notable effect on hearing speech, therefore hearing aids are often beneficial.

    “This combination has a notable effect on hearing speech, therefore hearing aids are often beneficial.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Estrogen deficiency may contribute to sensorineural hearing loss in TS, as supported by studies of inner ear pathology in estrogen receptor beta knockout mice, although evidence in humans is lacking.

    “Finally, estrogen deficiency may contribute to sensorineural hearing loss as supported by studies of inner ear pathology in estrogen receptor beta knockout mice,659 although evidence in humans is lacking.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [659] Simonoska, 2009, Inner ear pathology and loss of hearing in estrogen receptor-beta deficient mice, J Endocrinol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Referral to lymphatic specialists such as physical therapists, occupational therapists, and lymphatic massage therapists can be useful for patients with persistent lymphedema.

    “Referral to lymphatic specialists such as physical therapists, occupational therapists, and lymphatic massage therapists can be useful for patients with persistent lymphedema.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Amelogenin, the gene encoding human enamel protein located on Xp22, is expressed on both sex chromosomes, explaining the thinner and hypoplastic enamel observed in TS.

    “Amelogenin, the gene encoding human enamel protein located on Xp22, is expressed on both sex chromosomes, explaining the thinner and hypoplastic enamel observed in TS.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Abnormal craniofacial development in TS leads to a less pronounced slope of the Eustachian tube, and muscular hypotonia impacts function of the soft palate and Eustachian tube opening, negatively affecting drainage of the middle ear and facilitating intrusion of microorganisms from the nasopharynx, resulting in a higher risk of middle ear effusions and infections.

    “Additionally, abnormal craniofacial development in TS leads to a less pronounced slope of the Eustachian tube, and muscular hypotonia impacts function of the soft palate and Eustachian tube opening. This negatively affects the drainage of the middle ear and facilitates intrusion of microorganisms from the nasopharynx, resulting in a higher risk of middle ear effusions and infections.655”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [655] Lim, 2020, Prevalence, risk factors and management strategies for otological problems in girls with Turner syndrome, Acta Paediatr source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Congenital anomalies of the kidney and urinary tract have been ascribed to a variety of genetic and environmental elements present at the time of renal development in utero that disrupt the fetal renal migration pattern, including possible lymphatic factors.

    “Congenital anomalies of the kidney and urinary tract have been ascribed to a variety of genetic and environmental elements present at the time of renal development in utero that disrupt the fetal renal migration pattern, including possible lymphatic factors.687”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [687] Nicolaou, 2015, Genetic, environmental, and epigenetic factors involved in CAKUT, Nat Rev Nephrol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the general population, around half of individuals with congenital anomalies of the kidney and urinary tract develop chronic renal insufficiency, a precursor to end-stage kidney disease.

    “In the general population, around half of individuals with congenital anomalies of the kidney and urinary tract develop chronic renal insufficiency, a precursor to end-stage kidney disease.689”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [689] Seikaly, 2003, Chronic renal insufficiency in children: the 2001 annual report of the NAPRTCS, Pediatr Nephrol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Renal ultrasound is useful to identify anatomical abnormalities; however, abnormalities may still be missed if not done by experienced technicians.

    “Renal ultrasound is useful to identify anatomical abnormalities; however, abnormalities may still be missed if not done by experienced technicians.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Genes on Xp related to beta-cell function and insulin signal transduction affect overall glucose metabolism and likely contribute to the risk of diabetes in TS, as illustrated by studies showing individuals with a 45,X karyotype or deletions of Xp to have a much higher incidence of diabetes compared to individuals with deletions isolated to Xq (17%-23% vs 9%).

    “Genes on Xp related to beta-cell function and insulin signal transduction affect overall glucose metabolism and likely contribute to the risk of diabetes in TS, as illustrated by studies showing individuals with a 45,X karyotype or deletions of Xp to have a much higher incidence of diabetes compared to individuals with deletions isolated to Xq (17%-23% vs 9%).630,703”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

    • cites [703] Bakalov, 2009, X-chromosome gene dosage and the risk of diabetes in Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The effect of GH on cardiometabolic health is contradictory, though leans toward benefit.

    “The effect of GH on cardiometabolic health is contradictory, though leans toward benefit.229,384”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [229] Baronio, 2017, The influence of GH treatment on glucose homeostasis in girls with Turner syndrome: a 7-year study, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Three main types of hepatic damage are described in TS: steatohepatitis, vascular damage mostly observed in regenerative nodular hyperplasia (RNH), and autoimmune disease.

    “Three main types of hepatic damage are described in TS: steatohepatitis, vascular damage mostly observed in regenerative nodular hyperplasia (RNH), and autoimmune disease.345”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [345] Roulot, 2004, Vascular involvement of the liver in Turner's syndrome, Hepatology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Risk factors for LFA in TS are age, obesity, insulin resistance, and Xq isochromosome.

    “Risk factors for LFA are age, obesity, insulin resistance, and Xq isochromosome, however even young children with TS without risk factors have a higher prevalence of LFA.342-344,714,715”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [342] Koulouri, 2008, Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [343] Singh, 2022, Hepatic abnormalities in youth with Turner syndrome, Liver Int source

      Not checked in the free run.

    • cites [344] Viuff, 2021, Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome—a nationwide cohort study, Aliment Pharmacol Ther source

      Not checked in the free run.

    • cites [714] Calanchini, 2018, Liver biochemical abnormalities in Turner syndrome: a comprehensive characterization of an adult population, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [715] Bourcigaux, 2023, Focus on liver function abnormalities in patients with Turner syndrome: risk factors and evaluation of fibrosis risk, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Recent studies suggest that FIB-4 scores are lower than expected in patients with TS, possibly reflecting that liver diseases are mild in most cases.

    “Recent studies suggest that FIB-4 scores are lower than expected in patients with TS,714,715 possibly reflecting that liver diseases are mild in most cases.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [714] Calanchini, 2018, Liver biochemical abnormalities in Turner syndrome: a comprehensive characterization of an adult population, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [715] Bourcigaux, 2023, Focus on liver function abnormalities in patients with Turner syndrome: risk factors and evaluation of fibrosis risk, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A FIB-4 score below 1.45 indicates a low risk of fibrosis and a score above 3.25 is in favor of advanced liver fibrosis.

    “A FIB-4 score below 1.45 indicates a low risk of fibrosis and a score above 3.25 is in favor of advanced liver fibrosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [718] Cusi, 2022, American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD), Endocr Pract source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The incidence of coeliac disease is increased in TS compared to the background female population, consistent with other autoimmune diseases.

    “The incidence of coeliac disease is increased in TS compared to the background female population consistent with other autoimmune diseases,344 although the mechanism remains speculative.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [344] Viuff, 2021, Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome—a nationwide cohort study, Aliment Pharmacol Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prevalence of coeliac disease increases with age and is highest in 45,X, 45,X/iso q or ring chromosome karyotypes where up to 7.5% have positive coeliac antibodies.

    “The prevalence of coeliac disease increases with age725,726 and is highest in 45,X, 45,X/iso q or ring chromosome karyotypes where up to 7.5% have positive coeliac antibodies.26,630”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [725] Marild, 2016, Turner syndrome and celiac disease: a case-control study, Pediatrics source

      Not checked in the free run.

    • cites [726] Naessén, 2024, Autoimmune disease in Turner syndrome in Sweden: an up to 25 years´ controlled follow-up study, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [26] Cameron-Pimblett, 2017, The Turner syndrome life course project: karyotype-phenotype analyses across the lifespan, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [630] Fiot, 2019, X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood, Eur J Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent metanalysis found approximately 1 in 22 individuals with TS have coeliac disease, with minimal difference if serology (3.4%) or biopsy (4.8%) is used for diagnosis.

    “A recent metanalysis found approximately 1 in 22 individuals with TS have coeliac disease,724 with minimal difference if serology (3.4%) or biopsy (4.8%) is used for diagnosis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [724] Al-Bluwi, 2021, Prevalence of celiac disease in patients with Turner syndrome: systematic review and meta-analysis, Front Med (Lausanne) source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several studies have shown that HRT is not deleterious to liver function in patients with TS and there may even be benefit.

    “Several studies have shown that HRT is not deleterious to liver function in patients with TS and there may even be benefit.344”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [344] Viuff, 2021, Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome—a nationwide cohort study, Aliment Pharmacol Ther source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The "dose effect" of the SHOX gene is associated with thinning of cortical bone and increased bone geometry at the distal radius.

    “Although karyotype per se737 is not predictive of BMD, the “dose effect” of the SHOX gene is associated with thinning of cortical bone and increased bone geometry at the distal radius.351,738,739”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [351] Soucek, 2018, A 6-year follow-up of fracture incidence and volumetric bone mineral density development in girls with Turner syndrome, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [738] Soucek, 2011, Bone geometry and volumetric bone mineral density in girls with Turner syndrome of different pubertal stages, Clin Endocrinol (Oxf) source

      Not checked in the free run.

    • cites [739] Schweizer, 2023, Normal bone density but altered geometry in girls with Turner syndrome, J Pediatr Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Danish registry study, anemia and gastrointestinal bleeding were not associated with IBD or celiac disease.

    “Interestingly anemia and gastrointestinal bleeding were not associated with IBD or celiac disease.344”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [344] Viuff, 2021, Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome—a nationwide cohort study, Aliment Pharmacol Ther source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    It is estimated that 23.8% of adults with TS have osteoporosis.

    “It is estimated that 23.8% of adults with TS have osteoporosis384 and a 25% increase in fracture rate exists.735,736”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [384] Gambineri, 2022, New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study, J Endocrinol Invest source

      Not checked in the free run.

304 of 304

  • The paper relies on this without support.

    TS affects multiple organs through all stages of life, necessitating multidisciplinary care.

    “TS affects multiple organs through all stages of life, necessitating multidisciplinary care.”

  • The paper relies on this without support.

    TS is usually accompanied by infertility due to premature ovarian insufficiency.

    “TS is usually accompanied by infertility due to premature ovarian insufficiency.”

  • The paper relies on this without support.

    TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, both observed with strikingly increased frequency in TS.

    “TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, both observed with strikingly increased frequency in TS.”

  • The paper relies on this without support.

    TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea.

    “TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea.”

  • The paper relies on this without support.

    Individuals with a deletion distal to Xq24 frequently have primary or secondary amenorrhea without short stature or other TS features and should be referred to as having premature ovarian insufficiency.

    “Those who have a deletion distal to Xq24 frequently have primary or secondary amenorrhea without short stature or other TS features and should be referred to as having premature ovarian insufficiency.”

  • The paper relies on this without support.

    Karyotyping is the gold standard test to diagnose TS.

    “Karyotyping is the gold standard test to diagnose TS.”

  • The paper relies on this without support.

    TS is associated with significant phenotypic variability ranging from individuals with classic traits to individuals without apparent observable traits.

    “TS is associated with significant phenotypic variability ranging from individuals with classic traits to individuals without apparent observable traits.”

  • The paper relies on this without support.

    Constitutional karyotype of individuals with prenatally diagnosed TS are uncertain, especially in patients with mosaicism.

    “Because constitutional karyotype of individuals with prenatally diagnosed TS are uncertain, especially in patients with mosaicism, postnatal confirmation by standard chromosome analysis performed on a peripheral blood sample is indicated, irrespective of prenatal ascertainment.”

  • The paper relies on this without support.

    A sufficient ovarian reserve to obtain sufficient embryos for testing is a prerequisite for applying pre-implantation genetic testing.

    “However, a sufficient ovarian reserve to obtain sufficient embryos for testing is a prerequisite for applying pre-implantation genetic testing.”

  • The paper relies on this without support.

    Missed and delayed diagnoses of TS continue to be a challenge.

    “Although there seems to be a tendency towards earlier diagnosis, missed and delayed diagnoses of TS continues to be a challenge.”

  • The paper relies on this without support.

    NIPT does not routinely include screening for sex chromosome abnormalities.

    “Despite the widespread use of NIPT, this does not routinely include screening for sex chromosome abnormalities necessitating postnatal recognition and testing.”

  • The paper relies on this without support.

    The later GH therapy is initiated, the larger the growth deficit and the lower the likelihood of normal adult stature.

    “In general, the later GH therapy is initiated, the larger the growth deficit and the lower the likelihood of normal adult stature.”

  • The paper relies on this without support.

    Karyotyping is the gold-standard technique for diagnosing TS.

    “While karyotyping is the gold-standard technique for diagnosing TS, it has major limitations as a screening tool.”

  • The paper relies on this without support.

    Karyotyping has major limitations as a screening tool, requiring specialized personnel, long processing time, and greater expense.

    “This requires specialized personnel and entails a long processing time and greater expense.”

  • The paper relies on this without support.

    Most girls with TS will require estrogen therapy to initiate or complete puberty prior to completion of linear growth.

    “Furthermore, as most girls with TS will require estrogen therapy to either initiate or complete puberty prior to completion of linear growth,”

  • The paper relies on this without support.

    Estrogen route, dose, and tempo of dose escalation impact pubertal growth and adult height.

    “the estrogen route, dose, and tempo of dose escalation will have an impact on pubertal growth and, therefore, on AH.”

  • The paper relies on this without support.

    Growth response to rhGH varies significantly across individuals.

    “as the growth response varies significantly across individuals.”

  • The paper relies on this without support.

    Short stature is a common feature and often the presenting concern leading to the diagnosis of TS.

    “Short stature is a common feature and often the presenting concern leading to the diagnosis of TS.”

  • The paper relies on this without support.

    The formulation, route, and dosing of childhood estrogen have not been optimized.

    “The formulation, route, and dosing of childhood estrogen have not been optimized.”

  • The paper relies on this without support.

    Height is only one of many factors that affect QoL in TS.

    “Height is only one of many factors that affect QoL in TS.”

  • The paper relies on this without support.

    Very low concentrations of serum E2 in healthy prepubertal girls have minimal impact on uterine growth.

    “Because very low concentrations of serum E2 in healthy prepubertal girls seem to have minimal impact on uterine growth”

  • The paper relies on this without support.

    Using physiological age as a guide to the initiation of hormone replacement therapy supports normal bone mineral accrual.

    “using physiological age as a guide to the initiation of HRT supports normal bone mineral accrual”

  • The paper relies on this without support.

    17β-estradiol is the natural physiological form of estrogen.

    “17β-estradiol (E2) is the natural physiological form of estrogen”

  • The paper relies on this without support.

    Ethinyl estradiol is a potent synthetic E2 analogue, widely used in the combined oral contraceptive pill and historically used as hormone replacement therapy in women with premature ovarian insufficiency including those with Turner syndrome.

    “Ethinyl estradiol is a potent synthetic E2 analogue, widely used in the combined oral contraceptive pill and, historically, has been used as HRT in women with premature ovarian insufficiency including those with TS.”

  • The paper relies on this without support.

    Ethinyl estradiol is long-acting; therefore, it cannot mimic the typical diurnal variation seen in early puberty, and serum concentration of E2 cannot be measured meaningfully while on ethinyl estradiol.

    “It is long-acting; therefore, it cannot mimic the typical diurnal variation seen in early puberty, and serum concentration of E2 cannot be measured meaningfully while on ethinyl estradiol.”

  • The paper relies on this without support.

    Transdermal patches may fail to adhere well in girls with skin conditions such as eczema and may also cause skin irritation, both limiting their use.

    “However, TD patches may fail to adhere well in girls with skin conditions such as eczema and they may also cause skin irritation, both limiting their use.”

  • The paper relies on this without support.

    Tablets are available in fixed doses, and it is difficult to divide into smaller doses.

    “However, a drawback is that tablets are available in fixed doses, and it is difficult to divide into smaller doses.”

  • The paper relies on this without support.

    The lowest dose available is 0.5 mg but is only available in a few countries.

    “The lowest dose available is 0.5 mg but is only available in a few countries.”

  • The paper relies on this without support.

    It has not been shown scientifically whether any route is superior to the other in a lifelong replacement situation in Turner syndrome or in any other hypogonadal group.

    “Even though the transdermal route is theoretically attractive, it has not been shown scientifically whether any route is superior to the other in a lifelong replacement situation in TS or in any other hypogonadal group.”

  • The paper relies on this without support.

    In early puberty there is a diurnal variation with E2 serum concentrations increasing first during night-time and very early morning; in mid-puberty, the diurnal variation ceases, and serum E2 concentrations increase until menarche followed by the estradiol–progesterone cyclic variation of the adult fertile woman.

    “In early puberty there is a diurnal variation with E2 serum concentrations increasing first during night-time and very early morning. In mid-puberty, the diurnal variation ceases, and serum E2 concentrations increase until menarche followed by the estradiol–progesterone cyclic variation of the adult fertile woman.”

  • The paper relies on this without support.

    Estrogen has a dual effect on the growth plate: initially stimulatory but also leading to physeal fusion at higher concentrations.

    “estrogen has a dual effect on the growth plate: initially stimulatory but also leading to physeal fusion at higher concentrations.”

  • The paper relies on this without support.

    Ethinyl estradiol has been shown to be inferior to E2 for bone health after attainment of pubertal induction.

    “For estrogen replacement after attainment of pubertal induction, ethinyl estradiol has been shown to be inferior to E2 for bone health”

  • The paper relies on this without support.

    A standard oral contraceptive pill is taken for 21/28 days and a woman with Turner syndrome will therefore be hypoestrogenic during the pause.

    “It is useful to remember that a standard oral contraceptive pill is taken for 21/28 days and that a woman with TS will therefore be hypoestrogenic during the pause.”

  • The paper relies on this without support.

    The addition of progesterone administered in a cyclic regimen with estrogen allows regular, controlled, predictable episodes of withdrawal bleeding or “periods”.

    “Secondly, the addition of progesterone administered in a cyclic regimen with estrogen allows regular, controlled, predictable episodes of withdrawal bleeding or “periods”.”

  • The paper relies on this without support.

    Medroxyprogesterone acetate is effective at providing endometrial protection.

    “It is effective at providing endometrial protection.”

  • The paper relies on this without support.

    Medroxyprogesterone acetate also acts on the glucocorticoid receptor giving rise to potential glucocorticoid-like adverse effects, including an increased risk for breast cancer in non-Turner syndrome populations and stroke in postmenopausal women.

    “However, although it primarily acts on the PR, it also acts on the GR giving rise to potential glucocorticoid-like adverse effects, not shared with natural progesterone, including an increased risk for breast cancer in non-TS populations and stroke in postmenopausal women.”

  • The paper relies on this without support.

    The levonorgestrel intra-uterine device (LNG-IUS 52) is licensed for endometrial protection and contraception, has minimal side effects, and lasts for 5 years.

    “The levonorgestrel intra-uterine device (LNG-IUS 52) is licensed for endometrial protection and contraception. It has minimal side effects and lasts for 5 years.”

  • The paper relies on this without support.

    A continuous combined regimen is designed to avoid withdrawal bleeding which may not be attractive to young women and may also give rise to erratic vaginal bleeding, especially in those women using transdermal preparations.

    “However, such a regimen is designed to avoid withdrawal bleeding which may not be attractive to young women and may also give rise to erratic vaginal bleeding, especially in those women using TD preparations.”

  • The paper relies on this without support.

    A continuous combined regimen gives rise to an atrophic endometrium, and it is unclear whether this is a disadvantage in the short- or medium-term in women planning an oocyte-donated pregnancy.

    “A continuous combined regimen gives rise to an atrophic endometrium, and it is unclear whether this is a disadvantage in the short- or medium-term in women planning an oocyte-donated pregnancy.”

  • The paper relies on this without support.

    It is important not to underdose progesterone as that leads to more abnormal uterine bleeding.

    “It is important not to underdose progesterone as that leads to more abnormal uterine bleeding.”

  • The paper relies on this without support.

    Progesterone is unnecessary until uterine growth and development is approaching maturity.

    “Progesterone is unnecessary until uterine growth and development is approaching maturity.”

  • The paper relies on this without support.

    In girls undergoing pubertal induction, progesterone will likely be needed after about 1.5-3 years of unopposed estrogen administration or after the first episode of vaginal bleeding.

    “In girls undergoing pubertal induction, it is likely that progesterone will be needed after about 1.5-3 years of unopposed estrogen administration or after the first episode of vaginal bleeding.”

  • The paper relies on this without support.

    This ensures maximum time for uterine and breast development with unopposed estrogen.

    “This ensures maximum time for uterine and breast development with unopposed estrogen.”

  • The paper relies on this without support.

    Initial vaginal bleeding may be spotting only from an immature endometrium and does not necessarily indicate timing to start progesterone.

    “Initial vaginal bleeding may be spotting only from an immature endometrium and does not necessarily indicate timing to start progesterone.”

  • The paper relies on this without support.

    There are very few good quality studies of progesterone/progestins in pubertal induction or hormone replacement therapy in adolescents and women with Turner syndrome.

    “There are very few good quality studies of progesterone/progestins in pubertal induction or HRT in adolescents and women with TS.”

  • The paper relies on this without support.

    Studies of premature ovarian insufficiency tend to include many subjects with Turner syndrome and so this approach has some credence.

    “In practice, studies of premature ovarian insufficiency tend to include many subjects with TS and so this approach has some credence.”

  • The paper relies on this without support.

    Studies and trials describing the adverse effects of hormone replacement therapy invariably involve post-menopausal women, and extrapolation of results to young women with Turner syndrome is much more dubious and results should be regarded with great caution.

    “Studies and trials describing the adverse effects of HRT invariably involve post-menopausal women. In these cases, extrapolation of results to young women with TS is much more dubious and results should be regarded with great caution.”

  • The paper relies on this without support.

    There are also very few studies addressing compliance with and acceptability of hormone replacement therapy medication.

    “There are also very few studies addressing compliance with and acceptability of HRT medication.”

  • The paper relies on this without support.

    Social deprivation was a key influence on the availability of hormone replacement therapy treatment options but the reasons for this inequity are not understood.

    “Social deprivation was a key influence on the availability of HRT treatment options but the reasons for this inequity are not understood.”

  • The paper relies on this without support.

    HRT may improve quality of life and avoid the effects of estrogen deprivation, including vasomotor symptoms, urogenital effects, low BMD with increased fracture risk, cardiovascular disease with increased ischemic heart disease and stroke risk, and possible neurocognitive effects.

    “HRT may also help to improve QoL and to avoid the effects of estrogen deprivation including vasomotor symptoms, urogenital effects, low BMD with increased risk of fracture, cardiovascular disease with increased risk of ischemic heart disease and stroke and, finally, possible neurocognitive effects.”

  • The paper relies on this without support.

    Patient involvement in decisions about care improves adherence.

    “The need for individualized HRT, taking full account of patient preference is crucially important and patient involvement in decisions about care are known to improve adherence.”

  • The paper relies on this without support.

    Fear of side effects and financial constraints are among the reasons women stop HRT, even when evidence is given regarding poorer outcome for those without treatment.

    “Fear of side effects and financial constraints are among the reasons, even when evidence is given regarding poorer outcome for those without treatment.”

  • The paper relies on this without support.

    Prenatal or neonatal TTE may not definitively exclude BAV, anomalous pulmonary venous return, or variant aortic arch anatomy.

    “Even in the most experienced hands, prenatal or neonatal TTE may not definitively exclude BAV, anomalous pulmonary venous return, or variant aortic arch anatomy.”

  • The paper relies on this without support.

    Ultrasound image resolution is insufficient to distinguish small fetal cardiac structures such as the morphology of the aortic valve.

    “Ultrasound image resolution is insufficient to distinguish small fetal cardiac structures such as the morphology of the aortic valve.”

  • The paper relies on this without support.

    Unique features of the fetal circulation due to fetal shunts make prenatal detection of aortic coarctation difficult on the fetal echocardiogram.

    “In addition, there are unique features of the fetal circulation due to fetal shunts, such as patent foramen ovale and ductus arteriosus, that make prenatal detection of aortic coarctation difficult on the fetal echocardiogram.”

  • The paper relies on this without support.

    Postnatal development of aortic coarctation can only be completely ruled out once ductal closure is completed, which typically happens by 2 to 3 days of age.

    “Postnatal development of aortic coarctation can only be completely ruled out once ductal closure is completed, which typically happens by 2 to 3 days of age.”

  • The paper relies on this without support.

    Many individuals with TS are significantly smaller than age and sex matched controls in the general population.

    “Many individuals with TS are significantly smaller than age and sex matched controls in the general population.”

  • The paper relies on this without support.

    Acoustic shadowing tends to be more pronounced in TS and may significantly limit the sensitivity of TTE to detect potentially outcome-determining lesions.

    “Acoustic shadowing tends to be more pronounced in TS and may significantly limit the sensitivity of TTE to detect potentially outcome-determining lesions.”

  • The paper relies on this without support.

    CMR is less widely available compared to TTE and requires more extensive patient cooperation.

    “However, CMR is less widely available compared to TTE and requires more extensive patient cooperation.”

  • The paper relies on this without support.

    CT provides anatomical information of comparable quality to CMR during a much more rapid acquisition.

    “CT provides anatomical information of comparable quality to CMR during a much more rapid acquisition.”

  • The paper relies on this without support.

    CT involves radiation exposure, which is increased when ECG gating is used to obtain accurate aortic measurements.

    “However, CT involves radiation exposure, which is increased when ECG gating is used to obtain accurate aortic measurements.”

  • The paper relies on this without support.

    Hypertension can persist after coarctation repair, even in those without residual descending aortic pressure gradients.

    “Hypertension can persist after coarctation repair, even in those without residual descending aortic pressure gradients.”

  • The paper relies on this without support.

    Diagnosis of nocturnal hypertension can only be made by ambulatory blood pressure monitoring.

    “Diagnosis of nocturnal hypertension can only be made by ABPM.”

  • The paper relies on this without support.

    Outcome data about venous thrombosis are rare in TS, and a common underlying cause of thrombotic events has not yet been identified.

    “Outcome data about venous thrombosis are rare in TS, and a common underlying cause of thrombotic events has not yet been identified.”

  • The paper relies on this without support.

    There is no international consensus on when to begin lipid monitoring in individuals with TS.

    “There is no international consensus on when to begin lipid monitoring in individuals with TS.”

  • The paper relies on this without support.

    Newer research suggests that QTc prolongation may not be more prevalent among individuals with TS compared to the general population when defining prolongation as QTc >450 ms in girls and >460 ms in women using Hodges formula.

    “Newer research that was published after the 2016 guidelines suggests that QTc prolongation may not be more prevalent among individuals with TS compared to the general population when defining prolongation as QTc >450 ms in girls and >460 ms in women using Hodges formula.”

  • The paper relies on this without support.

    The risk of aortic dissection in TS is about 40:100 000 patient–years.

    “the low risk of aortic dissection in TS (about 40:100 000 patient–years)”

  • The paper relies on this without support.

    Cardiovascular demands of pregnancy are high due to increased cardiac output, stroke volume, heart rate, and plasma volume.

    “Cardiovascular demands of pregnancy are high due to increased cardiac output, stroke volume, heart rate, and plasma volume.”

  • The paper relies on this without support.

    After proximal aortic repair, women with TS are still considered to be at high risk for aortic dissections.

    “After proximal aortic repair, women with TS are still considered to be at high risk for aortic dissections.”

  • The paper relies on this without support.

    Beta-blockers do not cause fetal abnormalities.

    “Beta-blockers may be considered during pregnancy for women with aortic dilation (extrapolated from data for women with Marfan syndrome) and do not cause fetal abnormalities.”

  • The paper relies on this without support.

    Aortic dissection during pregnancy is a life-threatening complication that requires emergent cardiovascular specialist care.

    “Aortic dissection during pregnancy is a life-threatening complication that requires emergent cardiovascular specialist care.”

  • The paper relies on this without support.

    The maternal deaths reported in TS have been in oocyte donation pregnancies when IVF practitioners were unaware of TS implications.

    “The maternal deaths reported in TS have been in oocyte donation pregnancies when IVF practitioners were unaware of TS implications.”

  • The paper relies on this without support.

    There is a higher risk of complications, particularly cardiovascular complications, during pregnancy in individuals with TS.

    “Single embryo transfer is strongly recommended because of the higher risk of complications, particularly cardio-vascular complications during pregnancy.”
73 of 73

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Tenfold discrepancy in starting oral estradiol dose

    Major

    Table 4 gives the first-year oral E2 dose as 0.025 mg daily, while the practical guidelines summary recommends 0.25 mg daily as the starting dose.

  • Conflicting annual aortic dissection rates

    Major

    The cardiovascular section reports approximately 164 aortic dissections per 100,000 person-years in TS, but later describes the risk as about 40 per 100,000 patient-years. These are fourfold different rates for essentially the same time denominator.

  • Aortic size index has conflicting units

    Minor

    Table 13 labels ASI in cm per metre, whereas Table 12 defines it as aortic diameter in centimetres divided by body surface area in square metres.

  • Same cited guidelines assigned different years

    Minor

    The paper calls reference 1 the 2017 TS guidelines in one passage but the 2007 TS guidelines in another.

4 of 4

Cites

Flagged first, then by citations

76 of the 996 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Kollmann, 2016, Turner Syndrome: Growth Promoting Therapies, 201

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Authors
Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., Klein, K. O., Prakash, S. K., Shankar, R. K., Sandberg, D. E., Sas, T. C. J., Skakkebæk, A., Stochholm, K., van der Velden, J. A., The International Turner Syndrome Consensus Group, Alvarez-Nava, F., Avdic, H. B., Balle, C. M., Bamba, V., Bedei, I., Bonnard, Å., Brickman, W. J., Brown, N. M., Chernausek, S., Cobbold, J., Corathers, S. D., Corpechot, C., Crenshaw, M. L., Davies, M., Deeb, A., Dessens, A., Dowlut-McElroy, T., Elliott, V., Fadoju, D., Fechner, P. Y., Geffner, M., Gitomer, S., de Groote, K., Hewitt, J., Ho, C., Hutaff-Lee, C., Isojima, T., Johannsen, E. B., Kawai, M., Keselman, A., Knickmeyer, R. C., Kremen, J., Kristrøm, B., Kruszka, P., Law, J., Lin, A. E., Loechner, K., Mauras, N., Matthews, D., Mikkelborg, T., Mortensen, K. H., Nahata, L., Norman, M., Patel, S. R., Quigley, C., Ridder, L. O., Santen, R. J., Sheanon, N., Smyth, A., Turner, H., Verlinde, F., Viuff, M. H., Wasniewska, M., van der Weijde, B., Woelfle, J., Wolstencroft, J., & Backeljauw, P. F.
Affiliations
  • Aarhus University (DK)
  • Aalborg University Hospital (DK)
  • Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris , 75012 Paris , France
  • Children's Hospital Colorado (US)
  • Radboud University Medical Center (NL)
  • Medical University of Silesia (PL)
  • Area of Medical Genetics, Department of Translational Medicine, School of Medical Sciences, State University of Campinas , 13083-888 São Paulo , Brazil
  • Cincinnati Children's Hospital Medical Center, University of Cincinnati , Cincinnati, Ohio 45229 , United States
  • Department of Reproductive Medicine, Nij Geertgen Center for Fertility , Ripseweg 9, 5424 SM Elsendorp , The Netherlands
  • Stanford Medicine (US)
  • University of California San Diego (US)
  • The University of Texas Health Science Center at Houston (US)
  • Children's National (US)
  • University of Michigan (US)
  • Erasmus MC - Sophia Children’s Hospital (NL)
  • Department of Molecular Medicine, Aarhus University Hospital , 8200 Aarhus N , Denmark
  • Aarhus University Hospital (DK)
  • Department of Pediatric Endocrinology, Radboud University Medical Center, Amalia Children's Hospital , Nijmegen 6500 HB , The Netherlands
  • Central University of Ecuador (EC)
  • Cincinnati Children's Hospital Medical Center (US)
  • Khalifa University of Science and Technology (AE)
  • Children's Hospital of Philadelphia (US)
Corresponding author
  • Gravholt, Claus H
  • Backeljauw, Philippe F
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2024-05-15
Volume
190
Issue
6
Pages
G53-G151
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1093/ejendo/lvae050
PMC
PMC11759048
OpenAlex
W4396917273
Semantic Scholar
e69326a3dc0e3e1921efaf0f59e074d22ba2fc21
Cited by
224
References
996
Citations by year
2026: 87 · 2025: 111 · 2024: 25 · 2012: 1
FWCI
59.18
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Endocrinology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc)
  • HAL (submittedVersion, cc-by-nc)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by-nc)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by-nc)
Funders
  • Novo Nordisk Foundation (NNF15OC0016474, NNF20OC0060610, 2022–0189)
  • Independent Research Fund Denmark (0134-00406, 0134-00130B)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD093450)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Health Professions › Speech and Hearing › Adolescent and Pediatric Healthcare
Keywords
Turner syndrome, women and girls, multidisciplinary care, growth, puberty, estrogen therapy, cardiovascular health, transition to adult care, fertility assessment, comorbidities, health surveillance, neurocognitive function, neuropsychology, mental health, well-being
MeSH terms
Adolescent, Adult, Child, Europe, Female, Humans, Puberty, Turner Syndrome, Practice Guidelines as Topic

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